It is critical that applicants follow the instructions in the Research Instructions for the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this FOA is to invite applications to participate as a Core Clinical Center in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Core Clinical Centers can be either a single institution or a consortium of institutions coordinated through a lead institution. The mission of this Network is to advance hematopoietic cell transplantation (HCT) for patients with rare and difficult to treat blood diseases through high-quality multi-center clinical trials. This will be accomplished by evaluating new ways to improve traditional HCT approaches or by advancing HCT therapy through the use of either novel ex vivo manipulated cell products (e.g., cellular immunotherapy) or genetically-modified cells.

In the US, approximately 21,000 patients receive HCT annually for rare and diverse hematological indications. Most HCT centers conduct relatively small numbers of transplants (70% of centers transplant fewer than 50 patients), with less than half of the patients receiving cells from allogeneic donors. And although toxicity, unsatisfactory immune reconstitution, and even death may occur following HCT, transplant is the only curative option for many rare acquired and congenital blood diseases (e.g., severe aplastic anemia, sickle cell disease, thalassemia, immune deficiencies and bone marrow failure diseases) and hematological malignancies. Incorporation of new drugs, novel cell therapies or genetically-modified cells into HCT therapy may make transplant safer and more effective. However, not every patient eligible for HCT may benefit from this procedure because of a lack of an available matched donor. This is particularly true for minorities who are less likely than Caucasians to have a non-family member (allogeneic unrelated donor) who can provide available matched hematopoietic stem cells for transplant. While cord blood or haploidentical transplants may overcome the limitation of donor availability, HCT approaches using these donor sources require optimization to prevent graft failure, minimize graft versus host disease (GVHD), and reduce toxicity. Thus rare diseases, small patient populations in need of HCT, rapidly evolving HCT approaches, and the need to engage many centers to obtain sufficient patient numbers make HCT trials challenging. A clinical trials network provides a critical mass of investigators, increases patient availability and opportunity, and provides centralized and efficient approaches to conduct well-designed and well-coordinated trials.

The National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) have sponsored the BMT CTN since 2001. This Network has effectively addressed key issues for HCT, including donor availability, GVHD, post-transplant infection, disease control, organ and regimen-related toxicity, cost-effectiveness, and quality of life through the implementation of 37 trials, of which approximately half were Phase II and half Phase III. Many of these trials were guided by the scientific community input obtained through the Blood and Marrow Transplant Clinical Trials Network State of the Science Symposia conducted in 2007 and 2014. To advance HCT therapy, BMT CTN has collaborated with other networks and groups, including the NCI's cancer cooperative groups (currently the NCI Clinical Trials Network, or NCTN), NCI's AIDS Malignancy Consortium, the Canadian Blood and Marrow Transplant Group, the National Institute of Allergy and Infectious Diseases, the National Institute on Minority Health and Health Disparities, the NIH Office of Rare Diseases Research, and NHLBI's Sickle Cell Disease Clinical Research Network. In addition, the BMT CTN has implemented trials funded by NIH grants awarded to non-BMT CTN investigator teams as well as pharmaceutical companies. There are six to eight clinical studies active at all times. The Network's past and ongoing activities can be found at https://web.emmes.com/study/bmt2/.

During this funding cycle, the BMT CTN will direct more efforts toward the use of HCT and novel cell/gene therapies and to refining HCT approaches for non-malignant blood disorders. In particular, clinical studies that advance HCT approaches for non-malignant blood diseases and bone marrow failure syndromes where toxicity must be minimized will be considered key priorities. Trials evaluating ex vivo manipulated or genetically-modified cells in non-malignant and malignant blood diseases will be encouraged. Trials evaluating new approaches for stem cell mobilization, or that incorporate novel cell products to improve HCT safety and efficacy, reduce regimen-related toxicity and GVHD, and/or enhance immune function, will also be considered for implementation.

This FOA encourages applications to support up to 18 Core Clinical Centers, while a companion FOA will support the Data Coordinating Center (RFA-HL-17-019). Each Core Clinical Center is expected to enroll patients on BMT CTN trials, complete follow-up visits, analyze data from these trials, and disseminate the findings. Network funds will be available to support six to eight clinical trials to address the most important HCT problems for non-malignant blood diseases and hematological malignancies. The BMT CTN will be transitioned from a classic clinical trials network model into a flexible platform upon which studies funded by a variety of sources can be conducted. The network may also be leveraged to co-support trials addressing some broader clinical priorities, such as mitigating risks related to transfusion needs and thrombotic complications during HCT. The BMT CTN has already demonstrated the ability to forge public-private partnerships. It is expected that additional trials and ancillary studies will be conducted as collaborative studies funded through other means such as investigator-initiated R01s, industry, or relevant clinical trial groups. Trials comparing HCT with chemotherapy or evaluating maintenance therapy to control disease progression or relapse will be conducted in collaboration with the NCTN, usually with NCTN leading the trial.

To advance curative strategies for the clinic, it will be important to promote cross-fertilization between HCT physicians and pediatric hematologists, adult hematologists, and "cell therapy" experts who have expertise in ex vivo selection and expansion of cells, transgene expression, stem cell engineering, and genetic strategies to enhance immunity or cure blood diseases. This FOA is intended to support Core Clinical Centers that provide staff with complementary and integrated expertise, where a HCT physician is the Program Director/Principal Investigator (PD/PI), and at least one expert in non-malignant hematology or adoptive cell therapy is amongst the team members.

Protocols for ongoing BMT CTN clinical trials are listed on https://web.emmes.com/study/bmt2/. All new protocol topic areas supported by this FOA and its companion FOA for the Data Coordinating Center (DCC) will be decided cooperatively by the BMT CTN Steering Committee, comprised of each Core Clinical Center/Consortium PD/PI, the PD/PI of the DCC, and NHLBI and NCI staff. Two NHLBI-appointed Data Safety Monitoring Boards (DSMBs) will review all protocols before initiation and also advise NHLBI on research design issues, data quality and analysis, and ethical and human subjects protection matters.

The objective of the FOA is to invite Core Clinical Centers/Consortia applications with the scientific leadership to design and implement HCT trials in both non-malignant and malignant blood diseases, and trials that advance traditional HCT approaches through incorporation of ex vivo manipulated or genetically-modified cells. Core Clinical Centers must be willing and capable of enrolling patients to common BMT CTN protocols with the goal of providing answers through these studies more rapidly than individual centers.

This FOA seeks applications from Core Clinical Centers/Consortia able to:

1) Provide scientific leadership and expertise to develop BMT CTN-funded multi-center HCT trials in adults and children with non-malignant and malignant blood diseases, and HCT studies incorporating adoptive cell therapies including use of ex vivo modified cells and studies regulated by the Food and Drug Administration.

2) Identify, enroll, and retain participants in trials implemented by the current BMT CTN (https://web.emmes.com/study/bmt2/public/NewProtocol.html). These trials are consistent with research areas identified by the scientific community as priorities during the Blood and Marrow Transplant Clinical Trials Network State of the Science Symposia in 2007 and 2014.

3) Work collaboratively with non-BMT CTN funded investigators to enroll patients and conduct multi-center HCT trials that strategically address the emerging scientific opportunities in pediatrics, non-malignant blood diseases or novel cell and genetic therapies.

4) Efficiently conduct trials, proficiently manage all administrative activities, and disseminate results to the scientific community and patients in a timely manner.

5) Using past HCT history at the Core Clinical Center/Consortium and based on commitment from clinical team members, demonstrate that sufficient patients numbers are available for potential enrollment on BMT CTN studies.

Core Clinical Centers

Core Clinical Centers/Consortia are responsible for conducting HCT clinical trial protocols consistent with the mission of the BMT CTN. BMT CTN investigators are responsible for identifying, recruiting and retaining study subjects; entering data promptly and accurately into a web-based data collection system provided by the DCC; and contributing to manuscripts and otherwise disseminating research findings in a timely manner. Individual Core Clinical Centers should be prepared to participate in a cooperative and interactive manner with all network participants, the NHLBI, the NCI, and the DCC, as well as other collaborators. Protocols will be submitted as part of applications to this FOA. In conjunction with the DCC and Steering Committee (SC), Core Clinical Centers will be responsible for finalizing and prioritizing these protocols, developing common definitions and standardization across protocols, and analyzing and interpreting research results. Core Clinical Centers will also participate intellectually in all aspects of the Network governance, including developing Network procedures and subcommittees, finalizing clinical trial protocols and costs, developing a collaborative IRB process, and writing template informed consents. The PD/PI is directly responsible for ensuring that all aspects of BMT CTN protocols conducted at their Core Clinical Center/Consortium are being followed. The PD/PI will be expected to propose and conduct sub-studies and participate fully in Network committees. The PD/PI will be expected to develop regular communication with investigators and clinical coordinators from his/her Core/Consortium to identify and address enrollment, screening, adherence to protocols, and other Network issues.

The Core Clinical Centers will also be responsible for the planning and collection of high-quality biospecimens that will permit the longitudinal molecular analysis of disease pathogenesis and recovery, as well as disease stratification and mechanistic studies. These samples will be available to the wider scientific community for mechanistic work conducted under other funding mechanisms. Samples will be stored at a central laboratory repository at the DCC or at a subcontractor to the DCC.

Data Coordinating Center (DCC)

The DCC is supported by a separate award, described in detail in RFA-HL-17-019. In short, the DCC is responsible for the overall coordination and administration of the BMT CTN program; maintaining and updating the Manual of Operating Procedures; protocol finalization and prioritization, accrual plans and advertising materials for each BMT CTN trial; facilitating safety monitoring of Network trials; regulatory support; facilitating trials in rare hematological diseases and trials using novel cell therapies; tracking and compilation of data in secure data management systems, quality control, and data analyses; preparing minutes and reports for Network committees/subcommittees, and the NHLBI; identifying, qualifying and subcontracting with Affiliate transplant centers and other collaborators for BMT CTN clinical trials; reimbursing (per-patient) participating centers; subcontracting with a central laboratory responsible for the long-term storage, retrieval, and shipment of biospecimens; subcontracting with central laboratories as well as pharmaceutical companies for specific drugs and reagents; statistical supporting, study design, and data analyses; preparing data and safety reports for the DSMBs; coordinating manuscript and presentation development; and coordinating meetings and activities of the DSMBs, the BMT CTN Steering Committee, the External Advisory Committee, and other BMT CTN committees and subcommittees.

NHLBI & NCI

NHLBI and NCI staff are responsible for organizing and providing overall support for the BMT CTN. NHLBI Program staff and Office of Grants Management staff are responsible for the overall management of the grants for the Network. In addition to regular grant stewardship, the NHLBI and the NCI Project Scientists will be involved substantially with the awardees as a partner, consistent with the Cooperative Agreement mechanism.

Steering Committee (SC)

The SC will provide overall scientific governance for the BMT CTN and will be comprised of each Core Clinical Center/Consortium PD/PI, the PD/PI of the DCC, and NHLBI and NCI staff. A subcommittee from the SC nominates the Chair, but NHLBI reserves the right to approve the nomination and may otherwise appoint a Chair for the SC. The Chair rotates every two years. The SC formulates and implements all policy decisions related to the work of the BMT CTN and establishes its scientific agenda.

Protocols conducted during the project period may be one of those proposed by a funded Core Clinical Center PD/PI in an application to this FOA or may be a modified or combined version of one of these protocols. The SC will prioritize and select the protocol(s) to be conducted during the funding period from among those submitted in response to this FOA; the decision to fund a particular Core Clinical Center will not commit the BMT CTN to develop that Center's proposed protocol. All Core Clinical Centers are expected to participate in most of the protocols selected by the SC for the project period. The SC will appoint Protocol Teams, set timelines for protocol development and trial implementation, and ratify changes to the overall BMT CTN Manual of Procedures including updating to include procedures and guidelines for collaborative trials. The SC meets in-person up to three times annually and by teleconference monthly between the in-person meetings to monitor the progress of the Network and consider special issues that arise. Administrative support for the SC will be provided by the DCC.

Executive Committee (EC)

The EC and the DCC provide the day-to-day scientific management of the Network. The EC, a subset of the SC, will be comprised of the SC Chair, the immediate past Chair, the rising Chair, PD/PI(s) of the DCC, and the NHLBI and NCI Project Scientists. The EC sets the agenda for the SC meetings and calls, and makes the necessary day-to-day decisions between SC meetings.

External Advisory Committee (EAC)

An independent EAC, appointed by the NIH and funded through the DCC, will periodically review the activities of the BMT CTN and provide input on the direction and progress of the program to PD(s)/PI(s). The BMT CTN will have an opportunity to provide input on the expertise and responsibilities of the potential EAC members.

Data and Safety Monitoring Board (DSMB)

Two NHLBI-appointed DSMBs will monitor patient safety and review the performance of each study. As a part of their monitoring responsibility, the DSMBs submit recommendations to the NHLBI regarding the conduct and continuation of each clinical study.

Single Institutional Review Board of Record (sIRB)

The BMT CTN will utilize a single Institutional Review Board of Record (sIRB). An sIRB is expected to streamline IRB approvals, provide the ethical review, and maintain patient safety while reducing the inefficiencies and burden of each clinical site conducting their own IRB review. All BMT CTN Core Clinical Centers/Consortia members must agree to participate in a registered sIRB that will be engaged and implemented on the Network's behalf by the DCC.

Administrative & Technical Committees

The BMT CTN's scientific and administrative work is assisted by a variety of committees whose membership is drawn from the Core Clinical Centers, the DCC, staff from the NHLBI and the NCI, and additional experts as needed. Committees may include protocol development committees, a publications committee, a finance committee, a biospecimen and core lab committee, a clinical research associate committee, a pharmacy committee, and an ancillary studies committee. Other committees may be needed to support future BMT CTN activities, and members will be drawn from the Core Clinical Centers/Consortia awarded through this FOA or from the DCC and outside consultants, as needed.

Participation in BMT CTN Trials and Selection of new BMT CTN Trials

As per the intent of the NHLBI and NCI in supporting the BMT CTN, multiple trials will be conducted during the project period. It is anticipated that each Core Clinical Center/Consortium will participate in BMT CTN trials that are currently enrolling. Additionally, protocols will be selected and developed by the SC from the protocols proposed in applications to this FOA by the awarded Core Clinical Centers. Trials for non-malignant blood diseases that include mechanistic studies are encouraged.

The BMT CTN FOAs will support the network infrastructure for seven years and anticipate that up to eight new BMT CTN trials or studies may be initiated, launched, and completed during that period. The exact number of protocols and mechanistic studies supported in the program will depend on the nature and extent of the investigations proposed and on available funds. Protocols proposed in applications to this FOA should be completed during this funding cycle.

Additional new protocols supported through collaborations with R01-funded investigators, other clinical trial groups, or pharmaceutical companies may be implemented by the BMT CTN as appropriate. As protocols are developed, support will depend upon the availability of funds, and per-patient funding made available through agreements with the DCC. It is anticipated that each Core Clinical Center/Consortium will be able to participate in most of the protocols or enroll at least 18 participants to BMT CTN trials annually. Up to eight new clinical trials led by the BMT CTN will be reviewed by a sIRB established for the Network; clinical trials conducted in collaboration with the NCTN and led by the NCTN will be reviewed by an NCI central IRB.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the instructions in the Research Instructions for the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:
Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: 301-435-0270
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities and Other Resources: Applications should include sources of research support through departments, institutions, Clinical and Translational Science Awards (CTSAs), etc. Applications from institutions that have a CTSA funded by NIH should identify the resources that could be available to support the proposed Core Clinical Center, commenting particularly on those aspects that will enhance their programmatic and scientific efficiency. In such a case, a description of the CTSA and how the applicant proposes interacting with it should be included.

Document the availability and capacity of an institutional pharmacy capable of supporting clinical research.

Other Attachments: Attachments listed below must be provided or the application will not be peer reviewed, with the exception of the "Consortium Plan", which must only be provided if applicable.

Upload each attachment as a separate pdf file with the names specified below.

1. Transplant Center Activity

The filename "Transplant Center Activity.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. In a Table with columns for the calendar years 2013, 2014, and 2015, report the number of transplant recipients for the subgroups below:

1) Total

2) <18 years old

3) 18 years or older

4) with malignant blood diseases

5) with non-malignant blood diseases (include a footnote to the Table listing the diseases included in this number)

6) Race of HCT recipients: number of Caucasians, minorities, and unknown or not reported race

7) Autologous

8) Stem cells from HLA-matched siblings

9) Stem cells from other related donors

10) Stem cells from unrelated donors

11) Receiving peripheral blood stem cells as a graft source

12) Receiving bone marrow as a graft source

13) Receiving umbilical cord as a graft source

14) Enrolled in multi-center clinical trials

For an applicant proposing a consortium with more than one site, please combine the information from all sites into one table.

2. Clinical Research Capabilities

The filename "Clinical Research Capabilities.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. Provide an introduction to the table requested below that describes how the Core Clinical Center/Consortium team (i.e., physicians, translational cell therapists, nurses, coordinators) is positioned to support HCT trials for (a) pediatric patients, (b) adult patients, (c) patients with non-malignant blood diseases, (d) patients with hematological malignancies, (e) early phase trials and trials conducted under IND or IDE, and (f) trials evaluating novel cell therapies or genetically modified cells. After the introduction, applicants should provide a single Table with information demonstrating the Core Clinical Center's/Consortium's prior experience with multi-center HCT clinical research in adult and pediatric patients by listing all clinical trials conducted or completed over the past three years, highlighting the contributions from the proposed team.

The Table must include the following columns:

Column A: Name of the study/trial and ClinicalTrials.gov number

Column B: Brief description of the study/trial

Column C: Conducted under IND or IDE (yes or no)

Column D: Funding source(s). Please specify if from BMT CTN, other NIH support, industry and/or foundation/other

Column E: Applicant's role in trial (Study or Protocol PI/co-PI, Site PI, Site investigator, etc.)

Column F: Time from IRB approval to first patient enrolled

Column G: Participating site (or consortium member) and projected monthly enrollment for the site or proposed consortium

Column H: Actual monthly enrollment at the site or proposed consortium

Column I: Total number of participants needed across all sites

Column J: Publication reference

3. Enrollment Plan

The filename "Enrollment Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. Applications should include a detailed plan for prospective enrollment for BMT CTN 1101 (double cord vs haploidentical HCT for adults with leukemia); BMT CTN 1102 (HCT vs best therapy in adults with myelodysplastic syndrome); BMT CTN 1301 (calcineurin-free GVHD prophylaxis); BMT CTN 1302 (Allogeneic HCT and maintenance therapy for multiple myeloma); and BMT CTN 1503 (allogeneic HCT vs best therapy in adults with sickle cell disease) for the 15 month period beginning October 2017. Full protocols are posted on https://web.emmes.com/study/bmt2/public/NewProtocol.html. These trials are consistent with research areas identified by the scientific community as priorities during the Blood and Marrow Transplant Clinical Trials Network State of the Science Symposia in 2007 and 2014. The application should relate the enrollment plan information to the attachment "Transplant center activity.pdf" and to ongoing clinical trials at the Core or Consortium, and any specific limitations to enrolling patients to these trials.

4. Consortium Plan

A Consortium Plan is required only for applicants designating a Consortium as part of their application. The filename "Consortium Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. Without repeating information in the multiple PD/PI Leadership Plan, describe the rationale/benefit for including the specific sites that comprise the proposed Consortium including the aspects of the combined sites that will contribute significantly to scientific leadership of the BMT CTN (e.g., potential contributions to the BMT CTN administrative or technical committees). Communication and interactions among Consortium sites should be clearly documented. Describe the Consortium process for making decisions on scientific direction and procedures for resolving conflicts.

All instructions in the SF424 (R&R) Application Guide must be followed.

The PD/PI submitting this application must be a transplant physician experienced in the conduct of multi-center HCT trials for either adult or pediatric patients. The application should propose a multidisciplinary team, with at least one team member who is either a hematologist or cell therapist; other team members may include additional physicians, data managers, study coordinator(s), etc., and other individuals required to facilitate the implementation of all aspects of BMT CTN trials, including recruitment and retention of subjects. Applicants proposing a Consortium of sites must identify a Lead to oversee their site. All Key Personnel who are major contributors to the Core Clinical Center/Consortium must provide an NIH Biosketch whether or not they are budgeted.

All instructions in the SF424 (R&R) Application Guide must be followed.

Budgets must reflect support for personnel and infrastructure costs of the Core Clinical Center. The Core Clinical Center budget must include the effort required for Network participation, including regular teleconferences for discussion of protocols and other Network committees including regular SC conferences and technical committees, activities related to IRB approval and updates, manuscript preparation, and travel costs for in-person meetings. Other budgeted costs should include travel to attend an average of three SC meetings per year, two of which will be held in Washington, D.C., and the third likely to be held in conjunction with the annual CIBMTR/ASBMT meeting.

Core Clinical Centers should request funds for protocol set up and implementation that include personnel required for initial activities of the Network and support for the ongoing infrastructure and daily administrative and personnel needs.

Core Clinical Center infrastructure budget support is expected to consist of:

Personnel

• PD/PI and other key Physician Investigators: 1.2 person-months effort required (10 percent).
• Additional members of the Team, including a research nurse, coordinator, data entry personnel, and administrative support, as needed.

As part of the budget justification, applicants should estimate the total direct costs of implementing the protocol on a per-patient basis. An estimated protocol budget should be provided, as final costs will not be known until the SC selects and develops common protocols. Patient-related costs (e.g., clinical costs that are not part of routine clinical care such as laboratory tests, sample and data collection, supplies, drugs) will be distributed from the DCC budget in proportion to recruitment. Costs associated with equipment that may be unique to the proposed protocol must be included.

Enter the estimated costs for the proposed protocol as a line item in Section F. Other Direct Costs:

• Line 8 should be identified as protocol costs and should be entered under Funds Requested ($) in this line.

Examples of expenses associated with the conduct of a specific protocol that are considered part of the per-patient reimbursement include:

• Screening patients to determine study eligibility.
• Imaging studies, laboratory tests, and clinic visits that are not performed as part of routine clinical care.
• Expenses related to collecting biospecimens if required by protocol

Tests and clinic visits performed as part of routine clinical care can be incorporated into a research protocol, but their costs will be billed to third-party payers.

In the event that a central laboratory is required to analyze specimens, the Core Clinical Centers will be responsible for obtaining the sample(s); the cost of obtaining and shipping the sample(s) to a central laboratory will be part of the Core Clinical Center's per-patient reimbursement.

For trials implemented by the BMT CTN but funded primarily through collaborations with other clinical trial groups or networks, or R01-funded investigators, protocol budgets will be determined by the collaborator. Funding for trials supported using pharmaceutical company(ies) funds will be negotiated by the DCC on behalf of the BMT CTN, including the per-patient reimbursement.

Core Clinical Centers planning to participate on ongoing BMT CTN trials (see https://web.emmes.com/study/bmt2/) will have to accept protocol budgets and the per-patient reimbursement previously set by the current BMT CTN program.

NHLBI and NCI may make adjustments to a Center’s core budget based on accrual and the performance of that Core Clinical Center, using input from the Executive Committee and/or External Advisory Committee.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: The Research Strategy should include clear plans for participation as a Core Clinical Center in the BMT CTN. The Research Strategy should contain the four sub-sections (A-D) described below.

Sub-Section A. Organization and Governance

Provide an overview of the governance and organization of the research team at the Core Clinical Center/Consortium.

Describe the strategic advantage that will be achieved by the general expertise and the clinical services (i.e., hematology/oncology, hematology, pediatrics, or transplant) of the Core or Consortium as it pertains to the goals of the BMT CTN, including the experience and capabilities in novel cell therapies, genetically modified cells, and early phase trials. Describe the ability and commitment of the investigators to function as a coordinated research team, to work efficiently and expeditiously with other BMT CTN Core Clinical Centers/Consortia and the DCC to enhance the research goals of the BMT CTN and to enroll participants on trials with non-malignant and malignant blood diseases.

Include a plan for participating in the sIRB for BMT CTN trials.

Sub-Section B. Clinical Trial Capabilities for BMT CTN

Describe intended plans to leverage the Core Clinical Center's capabilities to address the scientific goals of the BMT CTN, including how the Core Clinical Center/Consortium team plans to be a contributing member of the BMT CTN.

Without repeating information from the Other Attachments, applicants must describe:

• How the proposed Core Clinical Center/Consortium plan to work together to facilitate and implement the current and future goals of the BMT CTN.
• Any state-of-the art scientific capabilities that may be shared or may be available and that may develop and expand the scientific productivity of the BMT CTN, such as experience in cell manufacturing, care for patients with non-malignant blood diseases including HCT for these disorders, or training and mentoring of junior physicians.
• Communication plans between the HCT, oncology and hematology services, and how clinical activities and responsibilities will be coordinated.
• Approach to selection and prioritization of BMT CTN clinical trials, including trials conducted in collaboration with other clinical trial groups, R01-funded investigators, and pharmaceutical companies.
• Approaches to recruit patients with rare non-malignant blood diseases, i.e., patient engagement or collaborations, and plans to include both genders, and racial and ethnic minorities as appropriate for the scientific goals of the research within the BMT CTN. Describe the referral base for patients with non-malignant blood diseases, if patients are routinely referred for HCT from outside the Core Clinical Center or Consortium.
• Plans for quality assurance, and complete and accurate transmission of data to the DCC to help minimize errors detected during site monitoring visits.
• Processes for responses to data entry edits and audits, including suggested timelines for responses.

Sub-Section C. Scientific Approach to HCT Trials

Applicants must:

• Use studies presented in Attachment 2, "Clinical Research Capabilities.pdf", or other recent studies to discuss key challenges, successes, and lessons learned from up to three trials/studies that struggled with recruitment and/or retention of subjects and up to three trials that enrolled and retained participants in the expected time frame.
• Describe any early phase HCT trials conducted by the Core Clinical Center or Consortium that led to a multi-center trial over the prior 5 or 6 years, and discuss challenges and lessons learned from this progression.

Sub-Section D. Scientific Direction

Identify a key scientific area that the BMT CTN should advance through a multi-center clinical trial. Provide a synopsis of a protocol that will be considered by the SC for full development and implementation as a BMT CTN trial as described in Section I and is consistent with the goals of this FOA.

The proposed protocol synopsis must:

• Address a significant unmet need in HCT, require multi-center implementation, and indicate the applicant’s knowledge of, and vision for, HCT research in the United States.
• Not replicate studies already conducted or undertaken by the current BMT CTN program (https://web.emmes.com/study/bmt2/), or being conducted or undertaken by an NCI Cancer Cooperative Group.
• Contain the hypotheses, background, rationale and available pilot data, basic study design, study population, treatment plan (type of HCT, conditioning, etc.), and statistical and feasibility considerations.
• Include a projected timeline for completing accrual to the study; accrual for proposed studies should take four years or less. Appropriate mechanistic/correlative studies linked to the application should be described, although funding for these studies will most likely have to be sought through other mechanisms.
• Address the appropriate inclusion of children and minorities as subjects, as well as any ethical issues related to the proposed trial as well as potential benefit(s) to human subjects.

Letters of Support: Letters of institutional and departmental support for participation in the BMT CTN are required and should include assurances that in the case of studies competing for the same patient population, BMT CTN studies will take priority. Applications proposing a consortium should include a letter of support from each site PI.

If an applicant plans to use their institutional CTSA funded by the National Center for Advancing Translational Research CTSA program, provide a letter of support from the CTSA PD/PI stating the specific CTSA resources that will be used.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Specific to this FOA:

• Awards issued under this FOA will be incrementally funded for up to 7 years. These will not be Multi-Year Funded.
• Awards issued under this FOA will be excluded from automatic carryover. All carryover actions will require NHLBI prior approval.
• Awards issued under this FOA will not be provided the authority to automatically extend the final budget period. All extensions, including the first, will require NHLBI prior approval.
• Awards issued under this FOA will be excluded from SNAP.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:

Does the proposed protocol synopsis address a significant unmet need or challenge an existing paradigm in blood and marrow transplantation for either malignant or non-malignant blood diseases or bone marrow failure syndromes? If mechanistic/correlative studies were proposed, how strongly will these advance the understanding of the underlying blood disease or advance the field?

What is the likelihood of success of the proposed plans to improve traditional HCT approaches or advance cell therapy with ex vivo manipulated cells or genetically-modified cells?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:

How strong are the scientific, administrative, clinical and academic qualifications of the PD/PI, and will these qualifications enable the PD/PI to lead the proposed team at the Core Clinical Center/Consortium to develop and implement BMT CTN trials? How strong is the demonstrated experience of the PD/PI with multi-center collaborative clinical trial research in adult or pediatric HCT?

How strong is the investigator team at the Core Clinical Center/Consortium in the field of HCT and non-malignant hematology, bone marrow failure disease or cell therapy? How well prepared is this team for conducting HCT trials in non-malignant blood diseases, in trials designed to minimize complications of HCT, and trials using either adoptive cell therapy including genetically-modified cells during transplant therapy, in addition to HCT trials for malignant blood diseases?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

Does the application describe how the Core Clinical Center/Consortium research team(s) will function together to conduct HCT trials that cross clinical areas (i.e., non-malignant blood diseases, or using novel cell products such as ex vivo expanded or genetically-modified cells)? What is the likelihood of success for the planned interaction? How strong is the communication and management plan for the Core Clinical Center/Consortium?

How strongly does the application demonstrate that the Core Clinical Center/Consortium has processes in place to recruit, retain, and clinically follow patients with diverse blood diseases in clinical studies?

What is the quality of the Core Clinical Center/Consortium's previous collaboration and depth of commitment to HCT research?

How thoroughly does the applicant discuss previous successes and challenges in recruiting each patient population?

How strongly does the application demonstrate its ability to promote the field of HCT conducted under regulations set by the Food and Drug Administration?

How strongly does the application support the ability of the Core Clinical Center/Consortium to address significant questions in the field of HCT by enrolling in BMT CTN trials already underway?

How strongly does the application support a willingness to participate in a sIRB model?

Are the plans described to include minorities, children and both genders appropriate for the goals of the BMT CTN? Have plans for recruitment and retention of subjects been adequately described?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA:

How strong are the administrative and research capabilities and patient base of the Core Clinical Center/Consortium in terms of participating in current and future activities of the BMT CTN, including in contributing patients with non-malignant diseases and as described in the FOA?

Does the applicant demonstrate that adequate patient populations exist for BMT CTN trials in both rare non-malignant blood diseases and hematological malignancies at the Core Clinical Center/Consortium, including patients with non-malignant blood diseases and minorities?

Does the applicant demonstrate evidence of commitment to prioritize BMT CTN trials?

Is there demonstrated adequacy of administrative and data management support for BMT CTN trials as described in the requirements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Transplant Center Activity:

Do the number of transplants and types of transplant recipients listed in the Transplant Center Activity attachment support the goals of the BMT CTN?

Clinical Research Capabilities:

Does the information provided in the Clinical Research Capabilities attachment demonstrate the applicant has adequate prior experience with multi-center collaborative HCT clinical research in adult and pediatric patients? Does the application bring experience in HCT for patients with non-malignant blood diseases or using adoptive cell therapies or genetically modified cells?

Enrollment Plan:

How strongly does the Enrollment Plan attachment support the commitment of the Core Clinical Center/Consortium to the ongoing trials BMT CTN 1101, BMT CTN 1102, BMT CTN 1301, BMT CTN 1302, and BMT CTN 1503? And if enrollment on these trials is not planned, is it well justified?

Consortium Plan:

If applicable, how strong are the plans for communication, decision making and conflict resolution between the core and collaborating sites as detailed in the Consortium Plan attachment?

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period.

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHLBI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NHLBI Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75 and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The BMT CTN program includes the Core Clinical Centers, a DCC, and staff from the NHLBI and the NCI. All Core Clinical Centers will be required to participate in a cooperative and interactive manner with one another and with the DCC. All awardees also agree to work collaboratively with the current Core Clinical Centers and the DCC to complete ongoing protocols. Awardees agree to the governance of the Network through a Steering Committee, and agree to work with the DCC, NHLBI, and NCI Staff to achieve the Network s objectives.

The Principal Investigators are responsible for the following: Accepting the coordinating role of the DCC and the participatory and cooperative nature of the Network process; Identifying new priority areas of research; Developing and implementing network clinical trials; Accurately projecting patient enrollment for each protocol during a specified timeframe; Collecting and submitting protocol-specific data to the DCC accurately and in a timely manner; Participating in data analysis and interpretation; Interpreting data and disseminating results through publications and presentations in a timely manner; Complying with the BMT CTN’s Manuals of Operations and all federally mandated regulatory requirements.

Core Clinical Centers are responsible for maintaining a high level of performance in the Network. Performance will be evaluated using the following criteria: Participation in BMT CTN clinical trials and meeting projected enrollment targets; Participation in research design and clinical trial protocol development, including serving as Chair of a clinical trial protocol or as a member of a protocol study team; participation in the scientific and administrative committees needed to support the BMT CTN s research objectives; Compliance with all applicable DHHS regulations concerning protection of human subject; Timely reporting of all serious and/or unexpected adverse events and all relevant medical information; Collection, processing, storage, and shipping of biospecimens per protocol specifications. Providing biospecimen-associated clinical data per protocol specifications; Serving as a resource for conduct of protocol-specified laboratory assays and ancillary studies, mechanistic, and biomarker studies. These projects may be supported by the BMT CTN, when approved by NHLBI, or by independent funding. Some of these projects may be conducted by the central laboratory which will be a subcontract from the DCC; and Other scientific contributions such as develop presentations and publications following the BMT CTN publication procedures.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. Data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators, within three years of the end of the period of NHLBI support, provided such release is consistent with the study protocol and governance and according to NHLBI Policy (http://www.nhlbi.nih.gov/research/funding/human-subjects/data-sharing).

Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. Participation by the third party; involvement of study resources, citing the name of the study or NHLBI support, or special access to study results, data, findings or resources requires notification and concurrence by NHLBI. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

Study PDs/PIs are encouraged to publish and disseminate results and other products of the study in accordance with study protocols and governance. For applicable studies, data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators, within three years of the end of the period of NHLBI support, provided such release is consistent with the study protocol and governance.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NIH Project Scientists will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, and will monitor patient recruitment and study progress, ensure disclosure of conflicts of interest, and ensure adherence to NHLBI policies. NHLBI will appoint Data and Safety Monitoring Boards (DSMBs). The Steering Committee Chair will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of Network activities and operations.

In addition to the NHLBI Project Scientist, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement, and will be identified in the Notice of Award. However, NHLBI may elect to have a dual-role approach where a single individual may act as the NHLBI Project Scientist and Project Officer. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. Because it is anticipated that the Project Scientist/Program Official will participate in activities that rise to a level of involvement that results in conflicts of interest, for example, co-publication, other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award.

The NHLBI reserves the right to phase-out or curtail trials (or an individual award) in the event of (a) failure to develop or implement mutually agreeable collaborative protocols; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c) major breach of the protocols or substantive changes in the agreed-upon protocols with which NHLBI cannot concur; (d) attaining of a major study endpoint before schedule with persuasive statistical significance; or (e) human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility include:

BMT CTN Steering Committee:

Awardee(s) agree to the governance of the study through a Steering Committee. The Steering Committee will have primary responsibility for identification of priority areas for research, the conduct of protocols, data analysis and the preparation of publications and dissemination products. The Steering Committee will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of Network activities and operations.

Steering Committee voting membership shall consist of all Principal Investigators (i.e., cooperative agreement awardees), one NHLBI Project Scientist, and one NCI Project Scientist. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee. All major scientific decisions will be determined by majority vote of the Steering Committee. The Steering Committee has final responsibility for approving the protocol before review by the DSMB. Technical Committees (i.e., Pharmacy, Publication) and subcommittees of the Steering Committee will be established as necessary. A protocol is the detailed written plan of a clinical experiment; DSMB reviews, NHLBI approval (with NCI consultation), FDA approval of IND or IDE (as appropriate), and IRB approvals are required prior to activating a clinical trial All study protocols must adhere to current NIH policies for human subjects research. All protocols must be approved by NHLBI. The PD/PIs will establish mutually agreed upon milestones with the steering committee for the development of each clinical research protocol and trial implementation; milestones may include such things as time to DSMB approval, time to a signed institutional contract for per-patient reimbursement, first patient enrolled, etc. Trial performance should be consistent with the NIH, and NHLBI policies, including the Milestone Accrual Policy. NHLBI will appoint and External Advisory Panel to advise on the performance of the network and the portfolio of trials conducted by the BMT CTN.

In-person meetings of the Steering Committee will ordinarily be held in the metropolitan Washington, D.C. area, up to three times a year, and by telephone conference call monthly. Steering Committee members must make every effort to attend Steering Committee meetings and participate in conference calls. Should the Lead PD/PI find it impossible to attend a Steering Committee meeting or conference call, he/she is required to notify the NHLBI Program Officer and/or Steering Committee Chair of the expected absence and ensure attendance by their designated alternate.

The Steering Committee and the DCC will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of Network activities and operations.

The NHLBI and NCI Project Scientists will serve on the Steering Committee and other study committees, when appropriate. The Project Scientists may work with awardees on issues coming before the Steering Committee such as recruitment, protocol development, follow-up, quality control, adherence to protocol, possible changes to the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment.

NHLBI-appointed DSMB:

The NHLBI Director appoints an independent DSMB advisory to the NHLBI that provides overall monitoring of interim data and safety issues. Meetings of the DSMB are ordinarily held in the metropolitan Washington, D.C. area. An Executive Secretary to the Board, other than the NHLBI Program Official, will be appointed by NHLBI to support the DSMB. Because the DSMB serves as an independent advisory group, study investigators should not communicate with the DSMB members regarding study issues, except as authorized by the DSMB’s Executive Secretary. The DSMB will consist of a chairperson and scientists with expertise in hematopoietic stem cell transplantation, bioethics, clinical research, clinical trial design, biostatistics, and other areas of expertise as needed. The DSMB will provide a written critique of each protocol and a final recommendation to the NHLBI. All study protocols must be reviewed and recommended by the DSMB and approved by the NHLBI before IRB submissions occur. The DSMB is also responsible for monitoring the clinical trials while they are being conducted with particular attention to safety issues.

Single Institutional Review Board of Record (sIRB):

In this renewal, the BMT CTN will utilize a single Institutional Review Board of Record (sIRB) for BMT CTN-led trials. A sIRB is expected to streamline IRB approvals, provide the ethical review, and maintain patient safety while reducing the inefficiencies and burden of each clinical site conducting their own IRB review. The DCC will engage and implement this board on the Network's behalf. The sIRB will carry out the functions required for institutional compliance with IRB review set forth in the HHS regulations at 45 CFR 46, and allow research to proceed as expeditiously as possible without sacrificing ethical principles and protections for participants enrolled in BMT CTN studies. Reliance agreements will delineate the respective authorities, roles, responsibilities and communication between the sIRB and the U.S. sites participating in BMT CTN-led trials. All BMT CTN Core Clinical Centers/Consortia members have to agree to participate in the registered sIRB engaged and implemented on the Network's behalf by the DCC.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Nancy L. DiFronzo, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0065
Email: [email protected]

William Merritt, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6137
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]

Jennifer Cho
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-6090
Email: [email protected]

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.