Description:
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
Title
- Brief Title: Family-mismatched/Haploidentical Donors Versus Matched Unrelated Donors
- Official Title: The Comparison of Transplantation From Family-mismatched/Haploidentical Donors With Matched Unrelated Donors in Adult Patients With Acute Myeloid Leukemia
Clinical Trial IDs
- ORG STUDY ID:
CBMTC-AML-1
- NCT ID:
NCT01751997
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Transplants from 8/8-matched Unrelated donors | | Transplants from 8/8-matched unrelated |
| Transplants from family-mismatched/haploidentical donors | | Transplants from family-mismatched/haploidentical donors |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Transplants from 8/8-matched unrelated | Active Comparator | Participants will receive transplants from 8/8-matched unrelated donors using myeloablative or reduced-intensity conditioning according to age or comorbidity. | - Transplants from 8/8-matched Unrelated donors
|
| Transplants from family-mismatched/haploidentical donors | Experimental | Participants will receive FMT using a reduced intensity conditioning regimens. | - Transplants from family-mismatched/haploidentical donors
|
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
| Maximum Eligible Age: | 65 Years |
| Minimum Eligible Age: | 17 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall survival |
| Time Frame: | annually through 3 years |
| Safety Issue: | |
| Description: | Overall survival is defined as the time interval between date of enrollment and death from any cause or for surviving patients, to last follow-up |
Secondary Outcome Measures
| Measure: | Neutrophil recovery |
| Time Frame: | 56 days |
| Safety Issue: | |
| Description: | defined as achieving an absolute neutrophil count greater than or equal to 500/mm^3 for three consecutive measurements on three difference days. The first of the 3 days will be designated the day of neutrophil recovery. |
| Measure: | Primary Graft failure |
| Time Frame: | 56 days |
| Safety Issue: | |
| Description: | defined as failure to achieve a neutrophil count greater than 500/mm^3 for 3 consecutive days at any time after transplantation. |
| Measure: | Secondary Graft failure |
| Time Frame: | 100 days |
| Safety Issue: | |
| Description: | defined as the development of an absolute neutrophil count less than 500/mm^3 after achievement of initial engraftment in the absence of recurrent disease. |
| Measure: | Platelet recovery |
| Time Frame: | 100 days and 180 days |
| Safety Issue: | |
| Description: | defined as the first day of a sustained platelet count greater than 20,000/mm^3 without platelet transfusions in preceding 7 days. The first day of the sustained platelet count will be designated the day of platelet engraftment. |
| Measure: | Donor cell engraftment |
| Time Frame: | 56 days |
| Safety Issue: | |
| Description: | Donor cell engraftment is defined as donor chimerism greater than or equal 5% on Day 56 after transplantation. Chimerism may be evaluated in whole blood or blood cell fractions, including cluster of differentiation (CD) 3 and CD33 or CD15 fractions. The actual measurement dates may be within +/- 7 days of the above recommended time points. |
| Measure: | Acute graft-versus-host disease (aGVHD) |
| Time Frame: | every 3 months through 3 years |
| Safety Issue: | |
| Description: | The cumulative incidence of aGVHD (grade II-IV and III-IV) will be determined. The time to onset of aGVHD will be recorded, as well as the maximum grade achieved. |
| Measure: | Chronic graft-versus-host disease (cGVHD) |
| Time Frame: | every 3 months through 3 years |
| Safety Issue: | |
| Description: | The cumulative incidence of cGVHD will be determined. Data will be collected directly from providers and chart review according to the recommendations of the NIH Consensus Conference. The NIH global severity scores of mild, moderate, and severe cGVHD will be assessed. |
| Measure: | Disease free survival |
| Time Frame: | annually through year 3 |
| Safety Issue: | |
| Description: | defined as the time interval from date of enrollment and time to relapse/progression, to death or to last follow-up |
| Measure: | Non-relapse mortality |
| Time Frame: | annually through year 3 |
| Safety Issue: | |
| Description: | The cumulative incidence of non-relapse mortality will be estimated at Days 100, 180, and at 1 and 2 years after transplantation. An event for this endpoint is death without evidence of disease progression or recurrence |
| Measure: | Infection |
| Time Frame: | annually through year 3 |
| Safety Issue: | |
| Description: | All grade 2 and 3 infections will be reported. Grade 1 cytomegalovirus infections through Day 56 will also be reported. |
| Measure: | WT1 MRD assessment |
| Time Frame: | before and 1 month after transplantation, then every 3 months through 3 years |
| Safety Issue: | |
| Description: | WT1 MRD assessment |
| Measure: | BAALC MRD assessment |
| Time Frame: | before and 1 month after transplantation, then every 3 months through 3 years |
| Safety Issue: | |
| Description: | BAALC MRD assessment |
| Measure: | NGS-based MRD assessment |
| Time Frame: | before and 1 month after transplantation, then every 3 months through 3 year |
| Safety Issue: | |
| Description: | NGS-based MRD assessment |
| Measure: | T cells reconstitution |
| Time Frame: | before and 2 weeks and 1 month after transplantation, then every 3 months through 1 year |
| Safety Issue: | |
| Description: | T cell subsets |
| Measure: | NK cells reconstitution |
| Time Frame: | before and 2 weeks and 1 month after transplantation, then every 3 months through 1 year |
| Safety Issue: | |
| Description: | NK cell subsets |
| Measure: | B cells reconstitution |
| Time Frame: | before and 2 weeks and 1 month after transplantation, then every 3 months through 1 year |
| Safety Issue: | |
| Description: | B cells |
Details
| Phase: | Phase 2/Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Byung-Sik Cho |
Last Updated
September 18, 2019
