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

October 3, 2021 updated by: Universitätsklinikum Hamburg-Eppendorf

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

Recruiting

Conditions

Intervention / Treatment

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 (Anticipated)

440

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Nicolaus Kröger, Prof. Dr.
  • Phone Number: +49 (0) 40 7410 55864
  • Email: n.kroeger@uke.de

Study Contact Backup

  • Name: Frauke Bach, Dr.
  • Phone Number: +49 (0) 40 7410 23182
  • Email: f.bach@uke.de

Study Locations

  • Austria
      • Graz, Austria, 8036
        • Recruiting
        • LKH-Univ. Klinikum Graz
        • Contact:
        • Principal Investigator:
          • Hildegard Greinix, Prof. Dr.
        • Sub-Investigator:
          • Heinz Sill, Prof. Dr.
      • Innsbruck, Austria, A-6020
        • Recruiting
        • Medizinische Universität Innsbruck
      • Wien, Austria, A-1090
        • Recruiting
        • Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT
        • Contact:
  • Czechia
      • Prague, Czechia, 128 20 Praha 2
        • Recruiting
        • Institute of Hematology and Blood Transfusion
        • Contact:
          • Markéta Marková, MUDr.
        • Contact:
          • Jana Brzonova
  • Finland
      • Turku, Finland, 20521
        • Recruiting
        • Turku University Central Hospital
        • Contact:
        • Principal Investigator:
          • Maija Itälä-Remes, Prof. Dr.
        • Sub-Investigator:
          • Urpu Salmenniemi, Prof. Dr.
  • Germany
      • Düsseldorf, Germany, 40225
        • Recruiting
        • University Hospital Düsseldorf
      • Essen, Germany, 45122
        • Recruiting
        • Universitätsklinikum Essen
        • Contact:
        • Principal Investigator:
          • Dietrich W. Beelen, Prof. Dr.
        • Sub-Investigator:
          • Rudolf Trenschel, Dr.
      • Frankfurt, Germany, 60590
      • Freiburg, Germany, 79106
        • Recruiting
        • Universitätsklinikum Freiburg
        • Contact:
        • Principal Investigator:
          • Jürgen Finke, Prof. Dr.
        • Sub-Investigator:
          • Hartmut Bertz, Prof. Dr.
      • Hamburg, Germany, 20246
        • Recruiting
        • Universitätsklinikum Hamburg-Eppendorf
        • Contact:
          • Nicolaus Kroeger, Prof. Dr.
          • Phone Number: +49 (0) 40 7410 55864
          • Email: n.kroeger@uke.de
        • Principal Investigator:
          • Nicolaus Kroeger, Prof. Dr.
      • Hannover, Germany, 30625
        • Recruiting
        • Medizinische Hochschule Hannover
        • Contact:
        • Principal Investigator:
          • Matthias Eder, Prof. Dr.
        • Sub-Investigator:
          • Gernot Beutel, Dr.
      • Leipzig, Germany, 04103
      • Münster, Germany, 48149
        • Recruiting
        • Universitatsklinikum Munster
        • Contact:
        • Sub-Investigator:
          • Jan-Henrik Mikesch, Dr.
      • Tübingen, Germany, 72076
  • Italy
      • Bergamo, Italy, 24127
  • Russian Federation
      • St. Petersburg, Russian Federation, 197022
        • Recruiting
        • Pavlov First Saint Petersburg State Medical University
        • Contact:
          • Sergey Bondarenko, MD, PhD
        • Contact:
          • Ivan Moiseev, MD, PhD
  • Spain
      • Badalona, Spain, 08916
        • Recruiting
        • Hospital Universitari Germans Trias i Pujol
        • Contact:
        • Principal Investigator:
          • Christelle Ferrà Coll, MD-PhD
      • Barcelona, Spain, 08041
        • Recruiting
        • Hospital de La Santa Creu i Sant Pau
        • Contact:
        • Principal Investigator:
          • Rodrigo Martino Bufarull, Dr.
      • Barcelona, Spain, 08036
        • Recruiting
        • Hospital Clínico y Provincial de Barcelona
        • Contact:
        • Principal Investigator:
          • Carmen Martínez Muñoz, Dr.
      • Madrid, Spain, 28007
      • Salamanca, Spain, 37007
        • Recruiting
        • Hospital Universitario de Salamanca
        • Contact:
        • Principal Investigator:
          • Dolores Caballero Barrigón, Dr.
      • Sevilla, Spain, 41013
      • Valencia, Spain, 46010
        • Recruiting
        • Hospital Clínico Universitario de Valencia
        • Contact:
        • Principal Investigator:
          • Carlos Solano, MD, PhD
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitario y Politécnico de La Fe
        • Contact:
        • Principal Investigator:
          • Jaime Sanz Caballer, Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

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
Time Frame: 2 years
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
Time Frame: 2 years
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
Time Frame: through study completion, an average of two yeras

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
Time Frame: Starting at day +30 (+/- 3 d) to 24 months (+/- 1 mo) after allogenic stem cell transplantation (SCT)
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
Time Frame: At 1 and 2 years after allogeneic SCT
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
Time Frame: On day +100 and 1 year (max grade) after allogeneic SCT
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
Time Frame: At 1 and 2 years after allogeneic SCT
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
Time Frame: through study completion, an average of two yeras
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
Time Frame: At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT
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
Time Frame: At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT
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
Time Frame: At baseline
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
Time Frame: At day 100, 6 months, 1 year and 2 years after allogenic SCT
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)
Time Frame: 2 years
Comparison of relapse incidence at two years between MRD positive and negative patients in both arms
2 years
Scientific Endpoint (optional)
Time Frame: 2 years
Comparison of overall survival at two years between MRD positive and negative patients in both arms
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitätsklinikum Hamburg-Eppendorf

Collaborators

Clinical Trial Center North (CTC North GmbH & Co. KG)
DKMS Stiftung Leben Spenden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 14, 2019

Primary Completion (ANTICIPATED)

November 1, 2022

Study Completion (ANTICIPATED)

November 1, 2024

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)

October 5, 2021

Last Update Submitted That Met QC Criteria

October 3, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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