Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia

NCT04232241 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: HaploMUDStudy
• Study Type: interventional
• Target: 167
• Locations: 7 countries
• Sites: 24

Brief Summary

Primary objective of this open label, two-arm, multicenter, multinational, randomized trial is to compare anti-leukemic activity of allogeneic stem cell transplantation for patients with acute leukemia in complete remission between a 10/10 HLA matched unrelated donor and a haploidentical donor. The hypothesis: Haploidentical stem cell transplantation with post cyclophosphamide induces a stronger anti-leukemic activity in comparison to 10/10 HLA matched unrelated donor and reduces the risk of relapse at 2 years after stem cell transplantation by 10%.

Conditions

Acute Myeloid Leukemia in Remission; Acute Lymphoblastic Leukemia in Remission; Myelodysplastic Syndromes

Keywords

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Allogeneic Stem Cell Transplantation; Matched Unrelated Allogeneic Stem Cell Transplantation; Haploidentical Allogeneic Stem Cell Transplantation; anti-leukemic activity; Cyclophosphamide as GVHD prophylaxis

Outcome Measures

Primary Outcomes (1)

• Relapse incidence at two years between both arms

  The primary efficacy endpoint will be analyzed using cumulative incidence estimation to assess the subdistribution hazard rates for both treatment groups at two years after accounting for competing risk events.

  2 years

Secondary Outcomes (11)

• Overall survival at two years between both arms

  2 years

• Overall survival for all patients assigned to one of the two treatment arms as time to event endpoint

  through study completion, an average of two yeras

• Comparison of GVHD/relapse-free survival as Composite endpoint in both arms

  Starting at day +30 (+/- 3 d) to 24 months (+/- 1 mo) after allogenic stem cell transplantation (SCT)

• Comparison of non-relapsed mortality (NRM) at 1 and 2 years after allogeneic SCT in both arms

  At 1 and 2 years after allogeneic SCT

• Comparison of acute graft-versus-host disease (aGVHD) on day +100 and 1 year (max grade) after allogeneic SCT according to the Glucksberg scale revised by Przepiorka et al. between both arms

  On day +100 and 1 year (max grade) after allogeneic SCT

Other Outcomes (2)

• Scientific Endpoint (optional)

  2 years

• Scientific Endpoint (optional)

  2 years

Study Arms (2)

Treatment A

ACTIVE COMPARATOR

Allogeneic stem cell transplantation from 10/10 HLA matched unrelated donor

Drug: Allogeneic Stem Cell Transplantation

Treatment B

EXPERIMENTAL

Allogeneic stem cell transplantation from haploidentical donor

Drug: Allogeneic Stem Cell Transplantation

Interventions

Allogeneic Stem Cell Transplantation DRUG

Allogeneic Stem Cell Transplantation

Treatment A; Treatment B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute Myeloid Leukemia (AML) intermediate or high risk according to ELN or Acute Lymphoblastic Leukemia (ALL) high risk according to ESMO guidelines in 1. CR or AML/ALL in 2. CR, or high risk MDS (according to IPSS-R) in 1. CR or 2. CR.
• Patients understand and voluntarily sign an informed consent form.
• ECOG ≤ 2.
• /10 HLA-matched unrelated donor and haploidentical (≥ 5/10 and ≤ 8/10 HLA) relative matched donor available at least 4 weeks after completion of induction and/or consolidation therapy.
• Females/Males who agree to comply with the applicable contraceptive requirements of the protocol.

You may not qualify if:

• Severe renal, hepatic, pulmonary or cardiac disease, such as:
• total bilirubin, SGPT or SGOT \> 3 times upper the normal level
• left ventricular ejection fraction \< 30 %
• creatinine clearance \< 30 ml/min
• DLCO \< 35 % and/or receiving supplementary continuous oxygen
• Positive serology for HIV.
• Pregnant or lactating women (positive serum pregnancy test).
• Age \< 18 and ≥ 71 years.
• Uncontrolled invasive fungal infection at time of screening (baseline).
• Serious psychiatric or psychological disorders.
• Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment.
• Uncontrolled severe autoimmune disease or uncontrolled other malignancy.
• Availability of an HLA-identical sibling as donor source.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• GKM Gesellschaft für Therapieforschung mbH: collaborator
• Staburo GmbH: collaborator

Study Sites (24)

LKH-Univ. Klinikum Graz

Graz, 8036, Austria

Location

Medizinische Universität Innsbruck

Innsbruck, A-6020, Austria

Location

Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT

Vienna, A-1090, Austria

Location

Institute of Hematology and Blood Transfusion

Prague, 128 20 Praha 2, Czechia

Location

Turku University Central Hospital

Turku, 20521, Finland

Location

University Hospital Düsseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Frankfurt am Main | Medizinische Klinik II

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Leipzig Dep. Innere Medizin, Neurologie und Dermatologie Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie

Leipzig, 04103, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

ASST Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

Hospital Universitari Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hospital Clínico y Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario y Politécnico de La Fe

Valencia, 46026, Spain

Location

Related Publications (1)

• Sanz J, Galimard JE, Labopin M, Afanasyev B, Sergeevich MI, Angelucci E, Kroger N, Koc Y, Ciceri F, Diez-Martin JL, Arat M, Sica S, Rovira M, Aljurf M, Tischer J, Savani B, Ruggeri A, Nagler A, Mohty M. Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT. J Hematol Oncol. 2021 May 28;14(1):84. doi: 10.1186/s13045-021-01094-2.

  PMID: 34049582 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Nicolaus Kröger, Prof. Dr.

  University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 18, 2020
• Study Start: November 14, 2019
• Primary Completion (Estimated): November 22, 2026
• Study Completion (Estimated): November 26, 2026
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); DE (9); IT (1); RU (1); ES (8); AU (3); CZ (1)