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

Acute Myeloid Leukemia Clinical Trial

— BMT CTN 1702  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03904134
• Other study ID #: BMT CTN 1702
• Secondary ID: 5U24HL138660-02N
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 14, 2019
• Est. completion date: March 2025

Study information

• Verified date: December 2023
• Source: Center for International Blood and Marrow Transplant Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1753
• Est. completion date: March 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

1. Patients of all ages with AML, ALL, MDS, NHL, HL, AA, or SCD are eligible.

2. Any planned conditioning regimen and GVHD prophylaxis approach is eligible.

3. 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.

4. Patient and physician must intend to proceed with allogeneic HCT within the next 6 months if a suitable donor is identified.

5. 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.

6. 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:

1. Prior allogeneic HCT (prior autologous transplant is allowed)

2. Previous formal unrelated donor search

Related Conditions & MeSH terms

• Acquired Aplastic Anemia
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Anemia, Aplastic
• Anemia, Sickle Cell
• Hodgkin Lymphoma
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Non-hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Sickle Cell Disease

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Rosewell Park Cancer Institute	Buffalo	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Mississippi	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of California, San Diego Medical Center	La Jolla	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Loyola University	Maywood	Illinois
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center - Adults	Omaha	Nebraska
United States	University of Nebraska Medical Center - Pediatrics	Omaha	Nebraska
United States	Memorial Healthcare System	Pembroke Pines	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford Hospitals and Clinics	Stanford	California
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	Children's National Medical Center	Washington	District of Columbia
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (6)

Lead Sponsor	Collaborator
Center for International Blood and Marrow Transplant Research	Blood and Marrow Transplant Clinical Trials Network, Medical College of Wisconsin, National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), National Marrow Donor Program

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival in patients transplanted for malignant diseases	To compare overall survival in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.	2 years
Other	Relapse in patients transplanted for malignant diseases	To compare relapse in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.	2 years
Other	Disease-free survival in patients transplanted for malignant diseases	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.	2 years
Other	Treatment-related mortality in patients transplanted for malignant diseases	To compare treatment-related mortality in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.	2 years
Other	Acute and chronic GVHD in patients transplanted for malignant diseases	To compare acute and chronic GVHD in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.	2 years
Other	Survival in patients with acquired aplastic anemia and sickle cell disease after transplantation	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.	2 years
Other	Acute and chronic GVHD in patients with acquired aplastic anemia and sickle cell disease after transplantation	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.	2 years
Other	AML or ALL in first complete remission or early stage MDS Substudy - QoL	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.	2 years
Other	AML or ALL in first complete remission or early stage MDS Substudy - primary graft failure	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.	2 years
Other	AML or ALL in first complete remission or early stage MDS Substudy - chronic GVHD	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.	2 years
Other	AML or ALL in first complete remission or early stage MDS Substudy - time until off systemic immunosuppression	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.	2 years
Other	AML or ALL in first complete remission or early stage MDS Substudy - GRFS	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.	2 years
Other	AML or ALL in first complete remission or early stage MDS Substudy - CRFS	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.	2 years
Other	AML or ALL in first complete remission or early stage MDS Substudy - current CRFS	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.	2 years
Other	QOL Substudy - number of hospital days	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.	2 years
Other	QOL Substudy - infections	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.	2 years
Other	QOL Substudy - immune reconstitution	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.	2 years
Other	QOL Substudy - late effects after transplantation	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.	2 years
Primary	Overall Survival for MUD Very Likely and MUD Very Unlikely Arms	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.	2 years
Secondary	Cumulative Incidence of Transplant by Donor Search Prognosis Score	To estimate and compare the cumulative incidence of receiving a transplant according to donor search prognosis, regardless of donor search prognosis	2 years
Secondary	Barriers to Transplant	To describe barriers to achieving transplantation with different donor search strategies, regardless of donor search prognosis	2 years