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| Name | Class |
|---|---|
| Gesellschaft für Therapieforschung mbH | INDUSTRY |
| Staburo GmbH | INDUSTRY |
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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%.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Active Comparator | Allogeneic stem cell transplantation from 10/10 HLA matched unrelated donor |
|
| Treatment B | Experimental | Allogeneic stem cell transplantation from haploidentical donor |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic Stem Cell Transplantation | Drug | Allogeneic Stem Cell Transplantation |
|
| 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 |
| 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 |
| 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 |
Inclusion Criteria
Exclusion Criteria
Severe renal, hepatic, pulmonary or cardiac disease, such as:
Positive serology for HIV.
Pregnant or lactating women (positive serum pregnancy test).
Age < 18 and ≥ 71 years.
Uncontrolled invasive fungal infection at time of screening (baseline).
Serious psychiatric or psychological disorders.
Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment.
Uncontrolled severe autoimmune disease or uncontrolled other malignancy.
Availability of an HLA-identical sibling as donor source.
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| Name | Affiliation | Role |
|---|---|---|
| Nicolaus Kröger, Prof. Dr. | University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| LKH-Univ. Klinikum Graz | Graz | 8036 | Austria | |||
| Medizinische Universität Innsbruck |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34049582 | Derived | 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. |
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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 |
| 2 years |
| Innsbruck |
| A-6020 |
| Austria |
| Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT | Vienna | A-1090 | Austria |
| Institute of Hematology and Blood Transfusion | Prague | 128 20 Praha 2 | Czechia |
| Turku University Central Hospital | Turku | 20521 | Finland |
| University Hospital Düsseldorf | Düsseldorf | 40225 | Germany |
| Universitätsklinikum Essen | Essen | 45122 | Germany |
| Universitätsklinikum Frankfurt am Main | Medizinische Klinik II | Frankfurt | 60590 | Germany |
| Universitätsklinikum Freiburg | Freiburg im Breisgau | 79106 | Germany |
| Universitätsklinikum Hamburg-Eppendorf | Hamburg | 20246 | Germany |
| Medizinische Hochschule Hannover | Hanover | 30625 | Germany |
| Universitätsklinikum Leipzig Dep. Innere Medizin, Neurologie und Dermatologie Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie | Leipzig | 04103 | Germany |
| Universitätsklinikum Münster | Münster | 48149 | Germany |
| Universitätsklinikum Tübingen | Tübingen | 72076 | Germany |
| ASST Papa Giovanni XXIII | Bergamo | 24127 | Italy |
| Pavlov First Saint Petersburg State Medical University | Saint Petersburg | 197022 | Russia |
| Hospital Universitari Germans Trias I Pujol | Badalona | 08916 | Spain |
| Hospital Clínico y Provincial de Barcelona | Barcelona | 08036 | Spain |
| Hospital de la Santa Creu I Sant Pau | Barcelona | 08041 | Spain |
| Hospital General Universitario Gregorio Marañón | Madrid | 28007 | Spain |
| Hospital Universitario de Salamanca | Salamanca | 37007 | Spain |
| Hospital Universitario Virgen del Rocío | Seville | 41013 | Spain |
| Hospital Clínico Universitario de Valencia | Valencia | 46010 | Spain |
| Hospital Universitario y Politécnico de La Fe | Valencia | 46026 | Spain |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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