Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia
- Conditions
- Acute Lymphoblastic Leukemia in RemissionAcute Myeloid Leukemia in RemissionMyelodysplastic Syndromes
- Interventions
- Drug: Allogeneic Stem Cell Transplantation
- Registration Number
- NCT04232241
- Lead Sponsor
- Universitätsklinikum Hamburg-Eppendorf
- 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%.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 167
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment B Allogeneic Stem Cell Transplantation Allogeneic stem cell transplantation from haploidentical donor Treatment A Allogeneic Stem Cell Transplantation Allogeneic stem cell transplantation from 10/10 HLA matched unrelated donor
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
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.
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.
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.
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.
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.
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.
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.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.
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.
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.
Trial Locations
- Locations (24)
LKH-Univ. Klinikum Graz
🇦🇹Graz, Austria
Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT
🇦🇹Wien, Austria
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria
Institute of Hematology and Blood Transfusion
🇨🇿Prague, Czechia
Turku University Central Hospital
🇫🇮Turku, Finland
University Hospital Düsseldorf
🇩🇪Düsseldorf, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Universitätsklinikum Frankfurt am Main | Medizinische Klinik II
🇩🇪Frankfurt, Germany
Universitätsklinikum Leipzig Dep. Innere Medizin, Neurologie und Dermatologie Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie
🇩🇪Leipzig, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
ASST Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Pavlov First Saint Petersburg State Medical University
🇷🇺St. Petersburg, Russian Federation
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
Universitätsklinikum Münster
🇩🇪Münster, Germany
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario y Politécnico de La Fe
🇪🇸Valencia, Spain