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

Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia With Identical GVHD Prophylaxis - A Randomized Prospective European Trial.

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%.

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia in Remission; Acute Lymphoblastic Leukemia in Remission
• Intervention / Treatment: Drug: Allogeneic Stem Cell Transplantation

Detailed Description

Secondary objectives are to assess and compare the safety and efficacy of study treatments therapy in both study arms on non-relapse mortality (NRM), relapse-free survival (RFS), Overall survival (OS), QOL, toxicity, development of acute and chronic GvDH as well as engraftment and chimerism and impact of measurable residual disease.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • LKH-Univ. Klinikum Graz
  • Innsbruck, Austria, A-6020
    • Medizinische Universität Innsbruck
  • Wien, Austria, A-1090
    • Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT
• Czechia
  • Prague, Czechia, 128 20 Praha 2
    • Institute of Hematology and Blood Transfusion
• Finland
  • Turku, Finland, 20521
    • Turku University Central Hospital
• Germany
  • Düsseldorf, Germany, 40225
    • University Hospital Düsseldorf
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt am Main | Medizinische Klinik II
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig Dep. Innere Medizin, Neurologie und Dermatologie Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
• Italy
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII
• Russian Federation
  • St. Petersburg, Russian Federation, 197022
    • Pavlov First Saint Petersburg State Medical University
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clínico y Provincial de Barcelona
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico de la Fe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. 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.
2. Patients age: 18 - 70 years at time of inclusion (female and male).
3. Patients understand and voluntarily sign an informed consent form.
4. ECOG ≤ 2.
5. 10/10 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.
6. Females/Males who agree to comply with the applicable contraceptive requirements of the protocol.

Exclusion Criteria

1. 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
2. Positive serology for HIV.
3. Pregnant or lactating women (positive serum pregnancy test).
4. Age < 18 and ≥ 71 years.
5. Uncontrolled invasive fungal infection at time of screening (baseline).
6. Serious psychiatric or psychological disorders.
7. Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment.
8. Uncontrolled severe autoimmune disease or uncontrolled other malignancy.
9. Availability of an HLA-identical sibling as donor source.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A; Allogeneic stem cell transplantation from 10/10 HLA matched unrelated donor	Drug: Allogeneic Stem Cell Transplantation; Allogeneic Stem Cell Transplantation
Experimental: Treatment B; Allogeneic stem cell transplantation from haploidentical donor	Drug: Allogeneic Stem Cell Transplantation; Allogeneic Stem Cell Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival at two years between both arms	The overall survival at two years between both arms will be presented with Kaplan-Meier's estimates of survival.	2 years
Overall survival for all patients assigned to one of the two treatment arms as time to event endpoint	The overall survival for all patients will be presented with Kaplan-Meier curve. To compare the survival distributions between two arms, log-rank test will be performed, and two-sided p-values will be presented. If applicable, Cox regression model stratified by the types of leukemia, types of complete remission and conditioning will be performed as sensitivity analysis.	through study completion, an average of two yeras
Comparison of GVHD/relapse-free survival as Composite endpoint in both arms	The rate of composite endpoint in both arms will be analyzed with the same methods as for the overall survival at two years between 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	Due to the existence of competing risk events (persisting disease and relapse), NRM of each arm at 1 and 2 years after allogeneic SCT will be analyzed with the same methods as for the primary endpoint	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	For each time point, the frequency and percentage of aGVHD (maximum grade) of each arm will be presented. To compare the difference between both arms, logistic regression adjusted for covariates and stratification factors will be performed.	On day +100 and 1 year (max grade) after allogeneic SCT
Comparison of chronic graft-versus-host disease (cGVHD) according to the NIH consensus criteria of Jagasia et al. at 1 and 2 years after allogeneic SCT between both arms	For each time point, the frequency and percentage of cGVHD of each arm will be presented. To compare the difference between both arms, logistic regression adjusted for the stratification factors will be performed.	At 1 and 2 years after allogeneic SCT
Comparison of toxicity of both regimens scored according to the current version of the NCI CTCAE between both arms	Safety will be analyzed with frequency of patients with AEs as described above.	through study completion, an average of two yeras
Comparison of immune reconstitution between both arms	Frequency and percentage of patients having immune reconstitution in two arms will be provided. For the comparison between two arms, logistic regression adjusted for the stratification factors will be performed.	At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT
Comparison of full donor chimerism between both arms	Frequency and percentage of patients having full donor chimerism in two arms will be provided. For the comparison between two arms, logistic regression adjusted for the stratification factors will be performed.	At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT
Evaluation of Sorror Risk Score on outcome after allogeneic SCT	Comorbidity score after Sorror will be assessed prior to randomization and outcome in both arms will be analyzed according the pre-transplant Sorror score.	At baseline
Comparison of QOL (FACT-BMT) before and after transplantation at + 100 days, 6 months, 1 year, 2 years between both arms	The means of change in scores at each time point (day 100, 6 months, 1 year and 2 years after transplantation respectively) from baseline and the confidence intervals of each arm will be presented. To compare the difference in QOL scores between both arms, logistic regression adjusted for covariates and stratification factors will be performed for each time point.	At day 100, 6 months, 1 year and 2 years after allogenic SCT

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scientific Endpoint (optional)	Comparison of relapse incidence at two years between MRD positive and negative patients in both arms	2 years
Scientific Endpoint (optional)	Comparison of overall survival at two years between MRD positive and negative patients in both arms	2 years

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: GKM Gesellschaft für Therapieforschung mbH; Staburo GmbH
• Investigators: Principal Investigator: Nicolaus Kröger, Prof. Dr., University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2019
• Primary Completion (Estimated): November 22, 2026
• Study Completion (Estimated): November 26, 2026

Study Registration Dates

• First Submitted: January 2, 2020
• First Submitted That Met QC Criteria: January 14, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• 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
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Precancerous Conditions; Bone Marrow Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Preleukemia; Myelodysplastic Syndromes
• Other Study ID Numbers: HaploMUDStudy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No