Clinical trial NCT03904134: Clinical Transplant-Related Long-term Outcomes of Alternative Donor Allogeneic Transplantation (BMT CTN 1702)
Official title: Clinical Transplant-Related Long-term Outcomes of Alternative Donor Allogeneic Transplantation (BMT CTN 1702)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndromes
Non-hodgkin Lymphoma
Hodgkin Lymphoma
Acquired Aplastic Anemia
Sickle Cell Disease
Lead sponsor: Center for International Blood and Marrow Transplant Research
Sponsor class: NETWORK
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Cancer Institute (NCI)
name: Blood and Marrow Transplant Clinical Trials Network
name: National Marrow Donor Program
name: Medical College of Wisconsin
First posted: 2019-04-05
Enrollment: 1753
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

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

Primary outcomes:
measure: Overall Survival for MUD Very Likely and MUD Very Unlikely Arms
timeFrame: 2 years
Secondary outcomes:
measure: Cumulative Incidence of Transplant by Donor Search Prognosis Score
timeFrame: 2 years
measure: Barriers to Transplant
timeFrame: 2 years
Other outcomes:
measure: Overall survival in patients transplanted for malignant diseases
timeFrame: 2 years
measure: Relapse in patients transplanted for malignant diseases
timeFrame: 2 years
measure: Disease-free survival in patients transplanted for malignant diseases
timeFrame: 2 years
measure: Treatment-related mortality in patients transplanted for malignant diseases
timeFrame: 2 years
measure: Acute and chronic GVHD in patients transplanted for malignant diseases
timeFrame: 2 years
measure: Survival in patients with acquired aplastic anemia and sickle cell disease after transplantation
timeFrame: 2 years
measure: Acute and chronic GVHD in patients with acquired aplastic anemia and sickle cell disease after transplantation
timeFrame: 2 years
measure: AML or ALL in first complete remission or early stage MDS Substudy - QoL
timeFrame: 2 years
measure: AML or ALL in first complete remission or early stage MDS Substudy - primary graft failure
timeFrame: 2 years
measure: AML or ALL in first complete remission or early stage MDS Substudy - chronic GVHD
timeFrame: 2 years
measure: AML or ALL in first complete remission or early stage MDS Substudy - time until off systemic immunosuppression
timeFrame: 2 years
measure: AML or ALL in first complete remission or early stage MDS Substudy - GRFS
timeFrame: 2 years
measure: AML or ALL in first complete remission or early stage MDS Substudy - CRFS
timeFrame: 2 years
measure: AML or ALL in first complete remission or early stage MDS Substudy - current CRFS
timeFrame: 2 years
measure: QOL Substudy - number of hospital days
timeFrame: 2 years
measure: QOL Substudy - infections
timeFrame: 2 years
measure: QOL Substudy - immune reconstitution
timeFrame: 2 years
measure: QOL Substudy - late effects after transplantation
timeFrame: 2 years
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: University of California, San Diego Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford Hospitals and Clinics
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Healthcare System
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center - Adults
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center - Pediatrics
state: Nebraska
city: Buffalo
country: United States
facility: Rosewell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Stephanie J Lee, MD, MPH
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: Stefan Ciurea, MD
role: STUDY_CHAIR
References: