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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04232241
Other study ID # HaploMUDStudy
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date November 14, 2019
Est. completion date November 2024

Study information

Verified date October 2021
Source Universitätsklinikum Hamburg-Eppendorf
Contact Nicolaus Kröger, Prof. Dr.
Phone +49 (0) 40 7410 55864
Email n.kroeger@uke.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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%.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 440
Est. completion date November 2024
Est. primary completion date November 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
Allogeneic Stem Cell Transplantation
Allogeneic Stem Cell Transplantation

Locations

Country Name City State
Austria LKH-Univ. Klinikum Graz Graz
Austria Medizinische Universität Innsbruck Innsbruck
Austria Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT Wien
Czechia Institute of Hematology and Blood Transfusion Prague
Finland Turku University Central Hospital Turku
Germany University Hospital Düsseldorf Düsseldorf
Germany Universitätsklinikum Essen Essen
Germany Universitätsklinikum Frankfurt am Main | Medizinische Klinik II Frankfurt
Germany Universitätsklinikum Freiburg Freiburg
Germany Universitätsklinikum Hamburg-Eppendorf Hamburg
Germany Medizinische Hochschule Hannover Hannover
Germany Universitätsklinikum Leipzig Dep. Innere Medizin, Neurologie und Dermatologie Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie Leipzig
Germany Universitätsklinikum Münster Münster
Germany Universitätsklinikum Tübingen Tübingen
Italy ASST Papa Giovanni XXIII Bergamo
Russian Federation Pavlov First Saint Petersburg State Medical University St. Petersburg
Spain Hospital Universitari Germans Trias I Pujol Badalona
Spain Hospital Clínico y Provincial de Barcelona Barcelona
Spain Hospital de la Santa Creu I Sant Pau Barcelona
Spain Hospital General Universitario Gregorio Marañón Madrid
Spain Hospital Universitario de Salamanca Salamanca
Spain Hospital Universitario Virgen del Rocío Sevilla
Spain Hospital Clínico Universitario de Valencia Valencia
Spain Hospital Universitario y Politécnico de La Fe Valencia

Sponsors (3)

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

Countries where clinical trial is conducted

Austria,  Czechia,  Finland,  Germany,  Italy,  Russian Federation,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Other Scientific Endpoint (optional) Comparison of relapse incidence at two years between MRD positive and negative patients in both arms 2 years
Other Scientific Endpoint (optional) Comparison of overall survival at two years between MRD positive and negative patients in both arms 2 years
Primary 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 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
Secondary 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
Secondary 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)
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
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