Clinical Transplant-Related Long-term Outcomes of Alternative Donor Allogeneic Transplantation (BMT CTN 1702) (BMT CTN 1702)

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ClinicalTrials.gov Identifier: NCT03904134

Recruitment Status : Active, not recruiting

First Posted : April 5, 2019

Last Update Posted : April 19, 2023

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Sponsor:

Collaborators:

National Heart, Lung, and Blood Institute (NHLBI)

National Cancer Institute (NCI)

Blood and Marrow Transplant Clinical Trials Network

National Marrow Donor Program

Medical College of Wisconsin

Information provided by (Responsible Party):

Center for International Blood and Marrow Transplant Research

Study Description

Brief Summary:

The purpose of this study is to determine if a search strategy of searching for an HLA-matched unrelated donor for allogeneic transplantation if possible then an alternative donor if an HLA-matched unrelated donor is not available versus proceeding directly to an alternative donor transplant will result in better survival for allogeneic transplant recipients within 2 years after study enrollment.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndromes Non-hodgkin Lymphoma Hodgkin Lymphoma Acquired Aplastic Anemia Sickle Cell Disease	Other: Donor Search Prognosis Score	Not Applicable

Detailed Description:

This is a multicenter, interventional and observational study to understand factors affecting the likelihood of transplantation in patients without a human leukocyte antigen (HLA) matched family donor and to compare outcomes associated with pursuing an HLA-identical unrelated versus other alternative donor graft sources. Alternative donors are defined as any donor other than an HLA-matched or 1 antigen-mismatched related donor. Patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), Non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), acquired aplastic anemia (AA) or sickle cell disease (SCD) are eligible. The primary comparison for the interventional study will be between two arms based on biologic assignment, analyzed on an intention-to-treat basis: Arm 1: Patients who are Very Likely to find a matched unrelated donor (MUD), defined as having a >90% chance of finding an 8/8 HLA-matched unrelated donor, for whom a fully matched unrelated donor will be pursued; and Arm 2: Patients who are Very Unlikely to find a MUD, defined as having a <10% chance of finding an 8/8 HLA-matched unrelated donor, for whom a haploidentical, cord blood, or mismatched unrelated donor transplant will be pursued. Patients with a Less Likely chance of finding a MUD, i.e., those not falling into the other two groups (a 26% chance), will be enrolled onto the observational component of the study and analyzed for all relevant endpoints but will not be included in the primary comparison.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1753 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	The primary comparison for the interventional study will be between two arms based on biologic assignment, analyzed on an intention-to-treat basis: Arm 1: Patients who are Very Likely to find a matched unrelated donor (MUD), defined as having a >90% chance of finding an 8/8 HLA-matched unrelated donor, for whom a fully matched unrelated donor will be pursued; and Arm 2: Patients who are Very Unlikely to find a MUD, defined as having a <10% chance of finding an 8/8 HLA-matched unrelated donor, for whom a haploidentical, cord blood, or mismatched unrelated donor transplant will be pursued. Patients with a Less Likely chance of finding a MUD, i.e., those not falling into the other two groups (a 26% chance), will be enrolled onto the observational component of the study and analyzed for all relevant endpoints but will not be included in the primary comparison.
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Clinical Transplant-Related Long-term Outcomes of Alternative Donor Allogeneic Transplantation (BMT CTN 1702)
Actual Study Start Date :	June 14, 2019
Estimated Primary Completion Date :	June 2024
Estimated Study Completion Date :	March 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Organ Donation

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Acute Lymphoblastic Leukemia Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Hodgkin Lymphoma Lymphoblastic Lymphoma Myelodysplastic Syndromes Sickle Cell Anemia Acute Graft Versus Host Disease Aplastic Anemia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Donor Search Prognosis: MUD Very Likely Patients who are Very Likely to find a matched unrelated donor (MUD), defined as having a >90% chance of finding an 8/8 HLA-matched unrelated donor, for whom a fully matched unrelated donor will be pursued.	Other: Donor Search Prognosis Score Patients will be placed on a study arm after receiving a Donor Search Prognosis Score, which is based on HLA allele frequencies and race/ethnicity. This score predicts the likelihood of successfully identifying a 10/10 matched unrelated donor.Worse search prognosis is associated with racial and ethnic minority status but not with other patient and disease biology characteristics that might influence the success of hematopoietic cell transplantation (HCT). Thus, the use of donor search prognosis in this trial as a tool for biologic assignment to matched unrelated donors vs. mismatched donors provides a mechanism to minimize bias from disease characteristics.
Donor Search Prognosis: MUD Very Unlikely Patients who are Very Unlikely to find a MUD, defined as having a <10% chance of finding an 8/8 HLA-matched unrelated donor, for whom a haploidentical, cord blood, or mismatched unrelated donor transplant will be pursued.	Other: Donor Search Prognosis Score Patients will be placed on a study arm after receiving a Donor Search Prognosis Score, which is based on HLA allele frequencies and race/ethnicity. This score predicts the likelihood of successfully identifying a 10/10 matched unrelated donor.Worse search prognosis is associated with racial and ethnic minority status but not with other patient and disease biology characteristics that might influence the success of hematopoietic cell transplantation (HCT). Thus, the use of donor search prognosis in this trial as a tool for biologic assignment to matched unrelated donors vs. mismatched donors provides a mechanism to minimize bias from disease characteristics.
Donor Search Prognosis: MUD Less Likely Patients with a Less Likely chance of finding a MUD, i.e., those not falling into the other two groups (a 26% chance), will be enrolled onto the observational component of the study and analyzed for all relevant endpoints but will not be included in the primary comparison.	Other: Donor Search Prognosis Score Patients will be placed on a study arm after receiving a Donor Search Prognosis Score, which is based on HLA allele frequencies and race/ethnicity. This score predicts the likelihood of successfully identifying a 10/10 matched unrelated donor.Worse search prognosis is associated with racial and ethnic minority status but not with other patient and disease biology characteristics that might influence the success of hematopoietic cell transplantation (HCT). Thus, the use of donor search prognosis in this trial as a tool for biologic assignment to matched unrelated donors vs. mismatched donors provides a mechanism to minimize bias from disease characteristics.

Outcome Measures

Primary Outcome Measures :

Overall Survival for MUD Very Likely and MUD Very Unlikely Arms [ Time Frame: 2 years ]
Compare overall survival between Very Likely to find a matched unrelated donor search prognosis patients and Very Unlikely to find a matched unrelated donor search prognosis patients who are evaluable.

Secondary Outcome Measures :

Cumulative Incidence of Transplant by Donor Search Prognosis Score [ Time Frame: 2 years ]
To estimate and compare the cumulative incidence of receiving a transplant according to donor search prognosis, regardless of donor search prognosis
Barriers to Transplant [ Time Frame: 2 years ]
To describe barriers to achieving transplantation with different donor search strategies, regardless of donor search prognosis

Other Outcome Measures:

Overall survival in patients transplanted for malignant diseases [ Time Frame: 2 years ]
To compare overall survival in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.
Relapse in patients transplanted for malignant diseases [ Time Frame: 2 years ]
To compare relapse in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.
Disease-free survival in patients transplanted for malignant diseases [ Time Frame: 2 years ]
To compare disease-free survival, treatment-related mortality, and acute and chronic GVHD in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.
Treatment-related mortality in patients transplanted for malignant diseases [ Time Frame: 2 years ]
To compare treatment-related mortality in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.
Acute and chronic GVHD in patients transplanted for malignant diseases [ Time Frame: 2 years ]
To compare acute and chronic GVHD in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.
Survival in patients with acquired aplastic anemia and sickle cell disease after transplantation [ Time Frame: 2 years ]
To describe survival in patients with acquired aplastic anemia and sickle cell disease after transplantation, according to the donor search prognosis and the alternative donor used.
Acute and chronic GVHD in patients with acquired aplastic anemia and sickle cell disease after transplantation [ Time Frame: 2 years ]
To describe acute and chronic GVHD in patients with acquired aplastic anemia and sickle cell disease after transplantation, according to the donor search prognosis and the alternative donor used.
AML or ALL in first complete remission or early stage MDS Substudy - QoL [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to compare QOL, according to the donor search prognosis and alternative donor used.
AML or ALL in first complete remission or early stage MDS Substudy - primary graft failure [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of primary graft failure, according to the donor search prognosis and alternative donor used.
AML or ALL in first complete remission or early stage MDS Substudy - chronic GVHD [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of chronic GVHD, according to the donor search prognosis and alternative donor used.
AML or ALL in first complete remission or early stage MDS Substudy - time until off systemic immunosuppression [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe time until off systemic immunosuppression, according to the donor search prognosis and alternative donor used.
AML or ALL in first complete remission or early stage MDS Substudy - GRFS [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of acute grade III-IV and chronic GVHD requiring immunosuppression-free, relapse-free survival (GRFS), according to the donor search prognosis and alternative donor used.
AML or ALL in first complete remission or early stage MDS Substudy - CRFS [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of moderate-severe chronic GVHD relapse-free survival (CRFS), according to the donor search prognosis and alternative donor used.
AML or ALL in first complete remission or early stage MDS Substudy - current CRFS [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of current CRFS (still on systemic treatment for cGVHD), according to the donor search prognosis and alternative donor used.
QOL Substudy - number of hospital days [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the number of hospital days in the first 100 post-transplant days, according to the donor search prognosis and alternative donor used.
QOL Substudy - infections [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of infections, according to the donor search prognosis and alternative donor used.
QOL Substudy - immune reconstitution [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of immune reconstitution, according to the donor search prognosis and alternative donor used.
QOL Substudy - late effects after transplantation [ Time Frame: 2 years ]
In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the late effects after transplantation, according to the donor search prognosis and alternative donor used.

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients fulfilling the inclusion criteria will be eligible for enrollment in this study. Of those who consent, only patients who lack a suitable HLA-identical or 1 allele or antigen mismatched related donors are evaluable. Patients with an HLA-identical sibling or 1 allele or antigen mismatched family member donor are evaluable as long as the center deems the family member donor as unsuitable for other reasons. Patients may co-enroll with other interventional or observational studies.

Patients of all ages with AML, ALL, MDS, NHL, HL, AA, or SCD are eligible.
Any planned conditioning regimen and GVHD prophylaxis approach is eligible.
Patients must be considered suitable allogeneic transplant candidates at the time of enrollment based on medical history, physical examination, and available laboratory tests. Specific testing for organ function is not required for eligibility but, if available, these tests should be used by the treating physician to judge transplant suitability.
Patient and physician must intend to proceed with allogeneic HCT within the next 6 months if a suitable donor is identified.
Center plans to follow the algorithm for alternative donor identification: (a) for subjects who are Very Likely to find a MUD, attempt to identify a matched unrelated donor; (b) for a subjects who are Very Unlikely to find a MUD, proceed expeditiously to a haploidentical, cord blood or mismatched unrelated donor.
Signed informed consent, and assent if applicable. Consent may be signed prior to completion of family typing but patients will only be considered evaluable upon confirmation that there is no suitable HLA-identical or 1 allele or antigen mismatched related donor available.

Exclusion Criteria:

Prior allogeneic HCT (prior autologous transplant is allowed)
Previous formal unrelated donor search

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03904134

Locations

Show 52 study locations

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United States, California
City of Hope
Duarte, California, United States, 91010
University of California, San Diego Medical Center
La Jolla, California, United States, 92093
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Stanford Hospitals and Clinics
Stanford, California, United States, 94305
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami
Miami, Florida, United States, 33136
Memorial Healthcare System
Pembroke Pines, Florida, United States, 33028
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
Emory University
Atlanta, Georgia, United States, 30322
Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Illinois
Loyola University
Maywood, Illinois, United States, 60153
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55414
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi
Jackson, Mississippi, United States, 39216
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
Washington University in St. Louis
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center - Adults
Omaha, Nebraska, United States, 68105
University of Nebraska Medical Center - Pediatrics
Omaha, Nebraska, United States, 68105
United States, New York
Rosewell Park Cancer Institute
Buffalo, New York, United States, 14263
Mount Sinai Medical Center
New York, New York, United States, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Children's Medical Center Dallas
Dallas, Texas, United States, 75235
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84113
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22903
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Center for International Blood and Marrow Transplant Research

National Heart, Lung, and Blood Institute (NHLBI)

National Cancer Institute (NCI)

Blood and Marrow Transplant Clinical Trials Network

National Marrow Donor Program

Medical College of Wisconsin

Investigators

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Study Chair:	Stephanie J Lee, MD, MPH	Fred Hutchinson Cancer Center
Study Chair:	Stefan Ciurea, MD	M.D. Anderson Cancer Center

Study Documents (Full-Text)

Documents provided by Center for International Blood and Marrow Transplant Research:

Study Protocol and Statistical Analysis Plan [PDF] December 10, 2018

Informed Consent Form [PDF] December 19, 2019

More Information

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Responsible Party:	Center for International Blood and Marrow Transplant Research
ClinicalTrials.gov Identifier:	NCT03904134
Other Study ID Numbers:	BMT CTN 1702 5U24HL138660-02 ( U.S. NIH Grant/Contract ) N00014-18-1-2888 ( Other Grant/Funding Number: Office of Naval Research )
First Posted:	April 5, 2019 Key Record Dates
Last Update Posted:	April 19, 2023
Last Verified:	April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Myelodysplastic Syndromes Anemia, Sickle Cell Anemia, Aplastic Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders	Immune System Diseases Bone Marrow Diseases Hematologic Diseases Leukemia, Lymphoid Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hemoglobinopathies Genetic Diseases, Inborn Bone Marrow Failure Disorders

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