Family-mismatched/Haploidentical Donors Versus Matched Unrelated Donors

NCT ID: NCT01751997

Last Updated: 2024-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2019-12-31

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Transplants from 8/8-matched unrelated

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

Group Type: ACTIVE_COMPARATOR

Transplants from 8/8-matched Unrelated donors

Intervention Type: DRUG

• 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

Transplants from family-mismatched/haploidentical donors

Participants will receive FMT using a reduced intensity conditioning regimens.

Group Type: EXPERIMENTAL

Transplants from family-mismatched/haploidentical donors

Intervention Type: DRUG

• 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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 17 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Byung-Sik Cho

OTHER

Sponsor Role: lead

Responsible Party

Byung-Sik Cho

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Hee-Je Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul St. Mary's Hematology Hospital

Locations

Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital

Seoul, , South Korea

Countries

South Korea

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Other Identifiers

CBMTC-AML-1

Identifier Type: -

Identifier Source: org_study_id