NCT01751997

Family-mismatched/Haploidentical Donors Versus Matched Unrelated Donors

The Comparison of Transplantation From Family-mismatched/Haploidentical Donors With Matched Unrelated Donors in Adult Patients With Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 116 (actual)
• Sponsor: Byung-Sik Cho · Academic / Other
• Sex: All
• Age: 17 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed 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.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Transplants from 8/8-matched Unrelated donors	* Myeloablative conditioning 1. Total body irradiation; 165 cGy, every 12 hours, 8 doses, days -7 to -4 (total 1320 cGy) 2. Cyclophosphamide; 60 mg/kg/day, IV for 30 minutes, days -3 to -2 (total 120 mg/kg) 3. Antithymocyte globulin (ATG); 1.25 mg/kg/day, IV for 6 hours, days -3 to -2, (total 2.5 mg/kg) * Reduced-intensity conditioning; older patients (age \> 55 years) and/or patients with comorbidities 1. Fludarabine; 30 mg/m\^2/day, IV for 1 hour, days -8 to -4 (total 150 mg/m\^2) 2. Busulfex; 3.2 mg/kg/day, IV for 3 hours, days -3 to -2 (total 6.4 mg/kg) 3. Total body irradiation; 200 cGy, every 12 hours 2 doses, days -1 (total 400 cGy) 4. ATG; 1.25 mg/kg/day, IV for 6 hours, days -3 to -2, (total 2.5 mg/kg) * GVHD prophylaxis 1. Tacrolimus; 0.03 mg/kg/day, IV for 24 hours from day -1 (0.12 mg/kg/day, PO, if tolerable) 2. Methotrexate; 5 mg/m\^2/day, IV push, days +1, +3, +6, +11
DRUG	Transplants from family-mismatched/haploidentical donors	* Reduced-intensity conditioning 1. Total body irradiation; 200 cGy, every 12 hours, 4 doses, days -9 to -8 (total 800 cGy) 2. Fludarabine; 30 mg/m\^2/day, IV for 1 hour, days -7 to -3 (total 150 mg/m\^2) 3. Busulfex; 3.2 mg/kg/day, IV for 3 hours, days -6 to -5 (total 6.4 mg/kg) 4. ATG; 1.25 mg/kg/day, IV for 6 hours, days -4 to -1 (total 5.0 mg/kg) * GVHD prophylaxis 1. Tacrolimus; 0.03 mg/kg/day, IV for 24 hours from day -1 (0.12 mg/kg/day, PO, if tolerable) 2. Methotrexate; 5 mg/m\^2/day, IV push, days +1, +3, +6, +11

Timeline

• Start date: 2013-01-01
• Primary completion: 2019-05-21
• Completion: 2019-12-31
• First posted: 2012-12-18
• Last updated: 2024-04-19

Locations

1 site across 1 country: South Korea