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

Sponsor
Universitätsklinikum Hamburg-Eppendorf (Other)
Overall Status
Recruiting
CT.gov ID
NCT04232241
Collaborator
DKMS Stiftung Leben Spenden (Other), Clinical Trial Center North (CTC North GmbH & Co. KG) (Other)
440
24
2
59.6
18.3
0.3

Study Details

Study Description

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%.

Condition or Disease Intervention/Treatment Phase
  • Drug: Allogeneic Stem Cell Transplantation
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
440 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia With Identical GVHD Prophylaxis - A Randomized Prospective European Trial.
Actual Study Start Date :
Nov 14, 2019
Anticipated Primary Completion Date :
Nov 1, 2022
Anticipated Study Completion Date :
Nov 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Relapse incidence at two years between both arms [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.

Secondary Outcome Measures

  1. Overall survival at two years between both arms [2 years]

    The overall survival at two years between both arms will be presented with Kaplan-Meier's estimates of survival.

  2. 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]

    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.

  3. 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)]

    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.

  4. 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]

    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

  5. 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]

    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.

  6. 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 [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.

  7. Comparison of toxicity of both regimens scored according to the current version of the NCI CTCAE between both arms [through study completion, an average of two yeras]

    Safety will be analyzed with frequency of patients with AEs as described above.

  8. Comparison of immune reconstitution between both arms [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.

  9. Comparison of full donor chimerism between both arms [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.

  10. Evaluation of Sorror Risk Score on outcome after allogeneic SCT [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.

  11. Comparison of QOL (FACT-BMT) before and after transplantation at + 100 days, 6 months, 1 year, 2 years between both arms [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.

Other Outcome Measures

  1. Scientific Endpoint (optional) [2 years]

    Comparison of relapse incidence at two years between MRD positive and negative patients in both arms

  2. Scientific Endpoint (optional) [2 years]

    Comparison of overall survival at two years between MRD positive and negative patients in both arms

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

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

  1. Positive serology for HIV.

  2. Pregnant or lactating women (positive serum pregnancy test).

  3. Age < 18 and ≥ 71 years.

  4. Uncontrolled invasive fungal infection at time of screening (baseline).

  5. Serious psychiatric or psychological disorders.

  6. Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment.

  7. Uncontrolled severe autoimmune disease or uncontrolled other malignancy.

  8. Availability of an HLA-identical sibling as donor source.

Contacts and Locations

Locations

Site City State Country Postal Code
1 LKH-Univ. Klinikum Graz Graz Austria 8036
2 Medizinische Universität Innsbruck Innsbruck Austria A-6020
3 Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT Wien Austria A-1090
4 Institute of Hematology and Blood Transfusion Prague Czechia 128 20 Praha 2
5 Turku University Central Hospital Turku Finland 20521
6 University Hospital Düsseldorf Düsseldorf Germany 40225
7 Universitätsklinikum Essen Essen Germany 45122
8 Universitätsklinikum Frankfurt am Main | Medizinische Klinik II Frankfurt Germany 60590
9 Universitätsklinikum Freiburg Freiburg Germany 79106
10 Universitätsklinikum Hamburg-Eppendorf Hamburg Germany 20246
11 Medizinische Hochschule Hannover Hannover Germany 30625
12 Universitätsklinikum Leipzig Dep. Innere Medizin, Neurologie und Dermatologie Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie Leipzig Germany 04103
13 Universitätsklinikum Münster Münster Germany 48149
14 Universitätsklinikum Tübingen Tübingen Germany 72076
15 ASST Papa Giovanni XXIII Bergamo Italy 24127
16 Pavlov First Saint Petersburg State Medical University St. Petersburg Russian Federation 197022
17 Hospital Universitari Germans Trias I Pujol Badalona Spain 08916
18 Hospital Clínico y Provincial de Barcelona Barcelona Spain 08036
19 Hospital de la Santa Creu I Sant Pau Barcelona Spain 08041
20 Hospital General Universitario Gregorio Marañón Madrid Spain 28007
21 Hospital Universitario de Salamanca Salamanca Spain 37007
22 Hospital Universitario Virgen del Rocío Sevilla Spain 41013
23 Hospital Clínico Universitario de Valencia Valencia Spain 46010
24 Hospital Universitario y Politécnico de La Fe Valencia Spain 46026

Sponsors and Collaborators

  • Universitätsklinikum Hamburg-Eppendorf
  • DKMS Stiftung Leben Spenden
  • Clinical Trial Center North (CTC North GmbH & Co. KG)

Investigators

  • Principal Investigator: Nicolaus Kröger, Prof. Dr., University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT04232241
Other Study ID Numbers:
  • HaploMUDStudy
First Posted:
Jan 18, 2020
Last Update Posted:
Oct 5, 2021
Last Verified:
Oct 1, 2021

Study Results

No Results Posted as of Oct 5, 2021