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

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ClinicalTrials.gov Identifier: NCT03904134
Recruitment Status : Not yet recruiting
First Posted : April 5, 2019
Last Update Posted : May 15, 2019
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

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1732 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)
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : March 2025


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.




Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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:
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

  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

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


Contacts
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Contact: Jenny Vogel 763-406-8691 jvogel@nmdp.org
Contact: Erin Leckrone eleckron@nmdp.org

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 Research 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:

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Responsible Party: Center for International Blood and Marrow Transplant Research
ClinicalTrials.gov Identifier: NCT03904134     History of Changes
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: May 15, 2019
Last Verified: May 2019
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
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Hodgkin Disease
Anemia, Sickle Cell
Anemia, Aplastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hemoglobinopathies
Genetic Diseases, Inborn