Randomized Clinical Study Assessing Haplo vs. URD in AML

NCT04067180 | Terminated DMC

• 1 other identifier: DNR: 2017/8
• Study Type: interventional
• Target: 18
• Locations: 5 countries
• Sites: 9

Brief 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

Keywords

allogeneic stem cell transplantation; Haplo-identical donors; Matched unrelated donors; Alternative stem cell donors; Post-transplantation cyclophosphamide; Haplo-identical stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• Intention to treat analysis of 2-year graft-vs.-host disease- and relapse-free survival

  Defined in this study as the time between inclusion and either grades III-IV acute GVHD, severe chronic GVHD or disease relapse. All events occuring from SCT to last follow-up are considered when calculating GRFS. Incomplete data resulting from patients who are lost to follow-up or who withdraw their informed consent will be censored at the date they were last known to be alive. Patients who are alive at study termination will be censored at the latest date of contact. Analysed according to original treatment arm assignment (intention-to-treat)

  2 years

Secondary Outcomes (15)

• Per protocol analysis of 2-year graft-vs.-host disease- and relapse-free survival

  2 years

• Intention to treat analysis of 5-year graft-vs.-host disease- and relapse-free survival

  5 years

• Per protocol analysis of 5-year graft-vs.-host disease- and relapse-free survival

  5 years

• Intention to treat analysis of Overall survival

  2 years and 5 years

• Intention to treat analysis of Disease-free survival

  2 years and 5 years

Study Arms (2)

Haplo SCT

EXPERIMENTAL

Allogeneic stem cell transplantation with a haplo-identical family donor graft.

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

URD SCT

ACTIVE COMPARATOR

Allogeneic stem cell transplantation with a matched unrelated donor graft.

Other: allogeneic stem cell transplantation with a matched unrelated donor graft

Interventions

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

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.

Haplo SCT

allogeneic stem cell transplantation with a matched unrelated donor graft OTHER

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.

URD SCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Adult patients (age ≥ 18 years) with de novo or treatment-related AML, eligible and fit for SCT treatment according to national/international guidelines.
• \. 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.
• \. Karnofsky Performance Status ≥ 70% at randomization.
• \. Signed informed consent.
• \. Patient willing and able to comply with protocol requirements

You may not qualify if:

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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Skane University Hospital: collaborator
• Uppsala University Hospital: collaborator
• University Hospital, Linkoeping: collaborator
• University Hospital, Umeå: collaborator
• Sahlgrenska University Hospital: collaborator
• Oslo University Hospital: collaborator
• St. Petersburg State Pavlov Medical University: collaborator
• Princess Margaret Hospital, Canada: collaborator
• Medical University of Vienna: collaborator

Study Sites (9)

Medical University of Vienna

Vienna, 1090, Austria

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Oslo University Hospital

Oslo, NO-0424, Norway

Location

Pavlov First Saint-Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

Sahlgrenska University Hospital

Gothenburg, SE-413 45, Sweden

Location

Linköping University Hospital

Linköping, SE-581 85, Sweden

Location

Skåne University Hospital

Lund, SE-221 85, Sweden

Location

Umeå University Hospital

Umeå, SE-901 85, Sweden

Location

Uppsala University Hospital

Uppsala, SE-751 85, Sweden

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Johan Karlsson Torlen, MD PhD

  Karolinska Institutet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 20, 2019
• First Posted: August 26, 2019
• Study Start: November 12, 2019
• Primary Completion: August 26, 2022
• Study Completion: August 26, 2022
• Last Updated: April 5, 2023

Record last verified: 2023-04

Locations

AU (1); NO (1); CA (1); RU (1); SE (5)