Randomized Clinical Study Assessing Haplo vs. URD in AML

Summary

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.

Conditions

• Acute Myeloid Leukemia

Interventions

OTHER

allogeneic stem cell transplantation with a haplo-identical family donor graft

The graft should preferably be bone marrow, but peripheral stem cells are also acceptable. Pre-conditioning: thiotepa 5 mg/kg/day for two days (day -6, -5), busulfan at 3,2 mg/kg/day (i.v.) and fludarabine at 50 mg/m2 (i.v.) for three consecutive days (day -4, -3, -2). Intravenous busulfan can be replaced by orally administered busulfan at a dose of 4 mg/kg/day on 3 consecutive days (day -4, -3, -2). GVHD prophylaxis: cyclophosphamide 50 mg/kg day +3 and +5, cyclosporin A and mycophenolate mofetil.

OTHER

allogeneic stem cell transplantation with a matched unrelated donor graft

Patients are treated according to the standard conditioning protocols developed for URD SCT at each participating center, with a recommendation to use "Flu+Bu" (fludarabine + busulfan, with a total Bu dose of 8-16 mg/kg body weight orally, or 6,4-12,8 mg/kg i.v.) or "Bu+Cy" (busulfan + cyclophosphamide, with a dose of Cy not exceeding 50 mg/kg x 2). The standard GVHD prophylaxis at the center should be applied.

Sponsors & Collaborators

• Skane University Hospital

  collaborator OTHER

• Uppsala University Hospital

  collaborator OTHER

• University Hospital, Linkoeping

  collaborator OTHER

• University Hospital, Umeå

  collaborator OTHER

• Sahlgrenska University Hospital

  collaborator OTHER

• Oslo University Hospital

  collaborator OTHER

• St. Petersburg State Pavlov Medical University

  collaborator OTHER

• Princess Margaret Hospital, Canada

  collaborator OTHER

• Medical University of Vienna

  collaborator OTHER

• Karolinska Institutet

  lead OTHER

Principal Investigators

• Johan Karlsson Torlen, MD PhD · Karolinska Institutet

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-11-12

Primary Completion

2022-08-26

Completion

2022-08-26

Countries

• Austria
• Canada
• Norway
• Russia
• Sweden

Study Locations