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

Sponsor

Center for International Blood and Marrow Transplant Research (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03904134

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Cancer Institute (NCI) (NIH), Blood and Marrow Transplant Clinical Trials Network (Other), National Marrow Donor Program (Other), Medical College of Wisconsin (Other)

1,753

Enrollment

Locations

Arms

68.6

Anticipated Duration (Months)

33.7

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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	N/A

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

Study Type:

Interventional

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.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 :

Jun 14, 2019

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: 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.
Other: 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.
Other: 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.

Arm

Intervention/Treatment

Other: 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.

Other: 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

Other: 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

Outcome Measures

Primary Outcome Measures

Overall Survival for MUD Very Likely and MUD Very Unlikely Arms [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	University of California, San Diego Medical Center	La Jolla	California	United States	92093
3	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
4	Stanford Hospitals and Clinics	Stanford	California	United States	94305
5	Children's National Medical Center	Washington	District of Columbia	United States	20010
6	University of Florida	Gainesville	Florida	United States	32610
7	University of Miami	Miami	Florida	United States	33136
8	Memorial Healthcare System	Pembroke Pines	Florida	United States	33028
9	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
10	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
11	Emory University	Atlanta	Georgia	United States	30322
12	Northside Hospital	Atlanta	Georgia	United States	30342
13	Loyola University	Maywood	Illinois	United States	60153
14	Indiana University	Indianapolis	Indiana	United States	46202
15	University of Maryland	Baltimore	Maryland	United States	21201
16	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
17	University of Michigan	Ann Arbor	Michigan	United States	48109
18	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
19	University of Minnesota	Minneapolis	Minnesota	United States	55414
20	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
21	University of Mississippi	Jackson	Mississippi	United States	39216
22	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
23	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
24	Washington University in St. Louis	Saint Louis	Missouri	United States	63110
25	University of Nebraska Medical Center - Adults	Omaha	Nebraska	United States	68105
26	University of Nebraska Medical Center - Pediatrics	Omaha	Nebraska	United States	68105
27	Rosewell Park Cancer Institute	Buffalo	New York	United States	14263
28	Mount Sinai Medical Center	New York	New York	United States	10029
29	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
30	University of North Carolina	Chapel Hill	North Carolina	United States	27599
31	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
32	Duke University Medical Center	Durham	North Carolina	United States	27710
33	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
34	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
35	Cleveland Clinic	Cleveland	Ohio	United States	44195
36	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
37	The Ohio State University	Columbus	Ohio	United States	43210
38	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
39	Oregon Health and Science University	Portland	Oregon	United States	97239
40	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
41	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
42	Medical University of South Carolina	Charleston	South Carolina	United States	29425
43	Children's Medical Center Dallas	Dallas	Texas	United States	75235
44	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
45	Baylor College of Medicine	Houston	Texas	United States	77030
46	M.D. Anderson Cancer Center	Houston	Texas	United States	77030
47	University of Utah	Salt Lake City	Utah	United States	84113
48	University of Virginia	Charlottesville	Virginia	United States	22903
49	Virginia Commonwealth University	Richmond	Virginia	United States	23298
50	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
51	University of Wisconsin	Madison	Wisconsin	United States	53792
52	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226