Randomized Clinical Study Assessing Haplo vs. URD in AML

This study compares haplo-identical family donor stem cell transplantation (haplo SCT) to matched unrelated donor transplantation (URD SCT) in adult patients with acute myeloid leukemia (AML) with the hypothesis that haplo SCT is as good as URD SCT. Background: A haplo-identical family donor is a relative sharing 50% of the human leukocyte antigens (HLA) of the patient. SCT with this type of donor is increasing, and a number of retrospective studies have demonstrated its feasibility, but prospective randomized studies are still lacking. Such studies are necessary to establish the benefits of haplo SCT. For the ≈70% of the patients that lack the 1st choice donor, an HLA-matched sibling, the 2nd choice is an URD at most centers. However, if haplo-identical donors are as good as URDs, this could change. Haplo-identical donors have several advantages. Almost all patients have at least one available haplo-identical donor, while URDs can be difficult to find. It also eliminates the need for time-consuming donor searches, and is considerably less costly. The Study: Patients can be included in the study if they have AML and require SCT, ≥18 years, DO NOT have an HLA-matched sibling donor, and DO have potential haplo-identical family donors AND URDs. After enrollment in the study, the patients are assigned randomly to either haplo SCT or URD SCT. The treatment surrounding the transplantation differs according to the donor type. Patients receiving haplo-identical transplantation are treated with a specified chemotherapy protocol before transplantation and a chemotherapy combined with immunosuppressive drugs after the transplantation to prevent graft-vs. host disease (GVHD). The patients receiving URD SCT will be treated according to the standard protocol at their center. Thus, haplo SCT will be compared to what is currently used in patients without an HLA-identical sibling today. The primary endpoint of this study is graft-vs.-host disease- and relapse free survival two years after study inclusion. This measurement takes into account the side effect that causes the most long-term suffering, graft-vs-host disease, as well as leukemia relapse and thus indicates to what extent the treated patients remain relapse-free and without significant side effects. Secondary end points include relapse-free survival, frequencies of graft-versus-host disease and of infections, and the patients will be followed in the study for five years.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* 1\. Adult patients (age ≥ 18 years) with de novo or treatment-related AML, eligible and fit for SCT treatment according to national/international guidelines.
* 2\. One or more potential haplo-identical related donor(s) AND five or more potential 6/6 HLA-A, -B, and -DRB1 antigen matched unrelated donors identified before randomization.
* 3\. Karnofsky Performance Status ≥ 70% at randomization.
* 4\. Signed informed consent.
* 5\. Patient willing and able to comply with protocol requirements

Exclusion Criteria:

* 1\. Patients with a suitable HLA-identical sibling donor.
* 2\. Patients with \< 5 potential HLA-A, -B, and -DRB1 antigen matched URDs available.
* 3\. Patients with no potential haplo-identical related donor available.
* 4\. Patients scheduled for/receiving cord blood stem cell transplantation.
* 5\. Prior allogeneic SCT using any hematopoietic stem cell source.
* 6\. Patients seropositive for HIV.
* 7\. Pregnancy (positive β-HCG test) within 4 weeks of study entry.
* 8\. Cardiac ejection fraction \< 45%.
* 9\. Karnofsky Performance Status \< 70% at time of randomization.
* 10\. The presence of any psychological, family-related, social, and/or geographical condition potentially jeopardizing compliance with the study protocol and follow-up schedule.