Family-mismatched/Haploidentical Donors Versus Matched Unrelated Donors
Conditions
Acute Myeloid Leukemia
Conditions: official terms
Leukemia, Myeloid - Leukemia, Myeloid, Acute
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Transplants from 8/8-matched Unrelated donors Type: Drug
Name: Transplants from family-mismatched/haploidentical donors Type: Drug
Overall Status
Recruiting
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 65 Years
Minimum Age: 17 Years
Gender: Both
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
Location
Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital
Seoul, Korea, Republic of
Status: Recruiting
Start Date
January 2013
Completion Date
December 2019
Sponsors
Seoul St. Mary's Hospital
Source
Seoul St. Mary's Hospital
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page