Family-mismatched/Haploidentical Donors Versus Matched Unrelated Donors

Byung-Sik Cho

Status and phase: Completed; Phase 3; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Transplants from 8/8-matched Unrelated donors; Drug: Transplants from family-mismatched/haploidentical donors

Study type: Interventional

Funder types: Other

Identifiers

NCT01751997

CBMTC-AML-1

Details and patient eligibility

About

This study will compare the clinical outcomes of transplants from family-mismatched/haploidentical donors (FMT) with transplants from 8/8-matched unrelated donor (MUT), which is a current gold standard donors when lacking of HLA-matched-siblings

1. Primary objectives: Overall survival of FMT may be similar to that of MUT

2. Secondary objectives:

   i. Comparison of disease-free survival, relapse, non-relapse mortality, immune reconstitution cytomegalovirus infection, and acute or chronic graft-versus-host disease between FMT and MUT.

   ii. Investigation of possible biomarkers related with above events after transplantation

Full description

For patients lacking an HLA-identical sibling, 8/8-matched unrelated donors are currently the "gold standard" for a donor, since outcomes after HLA-identical sibling have been compared to 8/8-matched unrelated donors. Currently, there are three alternative graft sources, including mismatched unrelated donors, familial mismatch/haploidentical donors, and umbilical cord bloods. Compared with other sources, transplants from familial mismatch/haploidentical donors (FMT) have the benefit of an immediate availability of a donor, particularly for those patients who urgently need transplantation. Initial reports had characterized FMT to a poor engraftment and a high incidence of graft-versus-host disease. However, outcomes of FMT have significantly improved over the past decade in the optimization of conditioning regimen and graft selection to allow a stable engraftment across major HLA barriers, with promising leukemia-free survival in adults with acute leukemia. Despite the encouraging results and potential benefit of FMT, there have been few studies comparing clinical outcomes of FMT with other donor types, particularly in acute myeloid leukemia (AML) as a single disease. Since August 2008, we have been continuously performing FMT using unmanipulated donor cells and a less aggressive conditioning regimen in high-risk AML lacking an HLA-identical sibling, 8/8 or 7/8-matched unrelated donors. We reported the feasibility of FMT using our novel reduced-intensity regimen without ex vivo T-cell depletion, showing early results similar to outcomes of transplant from 8/8-matched unrelated donors (MUT). This study will test the hypothesis that overall survival at 3 years after FMT is similar to overall survival after MUT.

Enrollment: 116 patients

Sex: All

Ages: 17 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Patients with AML aged from 18 to 65 years

• Eastern Cooperative Oncology Group (ECOG) performance < 2

• High risk group for relapse

  1. Complete remission (CR) 1 with unfavorable prognostic factor; presenting white blood cell > 100,000/microliter or prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or MDS/MPN or cytogenetics & molecular features (intermediate and adverse)
  2. CR2 or CR3 at transplantation

• No HLA-matched sibling and unrelated donor (HLA-A, -B, -C, and -DRB1)

• Acceptable organ function defined as serum creatinine < 2 mg/dl, unless considered due to leukemia and serum bilirubin < 3 mg/dl, unless considered due to leukemia

• Written informed consent form

Exclusion Criteria

• Active uncontrolled infections
• Corrected pulmonary diffusion capacity of <40%
• Cardiac ejection fraction of <35%
• ECOG performance status :2, 3, 4
• Active central nervous system involvement of disease
• Serological evidence of infection with HIV
• Pregnancy or breastfeeding
• Patient who are not suitable for the trial in accordance with principal investigator's decision

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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116 participants in 2 patient groups

Transplants from 8/8-matched unrelated

Active Comparator group

Description:

Participants will receive transplants from 8/8-matched unrelated donors using myeloablative or reduced-intensity conditioning according to age or comorbidity.

Treatment:

Drug: Transplants from 8/8-matched Unrelated donors

Transplants from family-mismatched/haploidentical donors

Experimental group

Description:

Participants will receive FMT using a reduced intensity conditioning regimens.

Treatment:

Drug: Transplants from family-mismatched/haploidentical donors