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The reason for the end of recruitment is that the recruitment target could not be achieved despite all efforts and the G-BA (financing party) does not consider a continuation of the AlloRelapseMM study to be expedient.
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| Name | Class |
|---|---|
| Gemeinsamer Bundesaussschuss | OTHER |
| Staburo GmbH | INDUSTRY |
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Allogeneic stem cell (allo SCT) transplantation for multiple myeloma is a potential curative treatment, but is associated with morbidity and treatment related mortality. Approved drug combinations or another autologous stem cell transplantation (auto-SCT) can be used for relapsed patients resulting in a median progression free survival up to 2-3 years.
In the current trial after first-line treatment relapsed or progressed myeloma patients with an HLA compatible donor will be randomized after 3 cycles of salvage therapy to allogeneic stem cell transplantation or to continuous conventional salvage therapy.
The primary objective of the present clinical study aims to demonstrate the superiority of allogeneic stem cell transplantation (allo SCT) compared to conventional therapy for the difference in overall survival (OS) at 5 years in patients with multiple myeloma who have relapsed or progressed after first-line autologous hematopoietic stem cell therapy.
The secondary objectives are to show an improvement of progression free survival and relapse free survival after allo SCT compared to conventional therapy.
In addition, quality of life, toxicities, recurrence rates, non-relapse mortality (NRM), remission rates including minimal residual disease (MRD) and incidence of severe or life-threatening infection between the two arms are compared. Acute and chronic graft-versus-host disease (GvHD) after allo SCT are evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (allo SCT) | Experimental | Allogeneic stem cell transplantation |
|
| Arm B (conventional therapy) | Active Comparator | Currently approved triple regimens for first relapse:
Alternatively, autologous stem cell transplantation may also be performed, if sufficient stem cells are still cryopreserved. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic Stem Cells | Drug | Allogeneic Stem Cell Transplantation |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival at five years after randomization | The present clinical study aims to demonstrate the superiority of allogeneic stem cell transplantation compared to conventional therapy for the difference in overall survival at 5 years in patients with multiple myeloma who have relapsed or progressed after first-line autologous hematopoietic stem cell therapy. | at 5 years after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Event-free survival at 1 year after randomization | A secondary objective is to show an improvement of progress free survival and relapse free survival after allogeneic stem cell transplantation compared to conventional therapy. Events are defined as:
| from randomization to 1 year after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Event-free survival at 3 and 5 years after randomization | Patients will be observed from randomization until database lock for interim analysis and the event-free survival (EFS) rate is calculated at 3 and 5 years after randomization. Events are defined as:
| from randomization to 3 and 5 years after randomization |
Inclusion Criteria:
Patients eligible for study inclusion must meet criteria 1- 7 at registration and all of the following criteria before randomization:
Exclusion Criteria:
Patients are excluded from the study if any one of criteria 1-6 are met at registration and if criterion 7 is met before randomization:
Non-sufficient organ function defined as:
Bilirubin (in the absence of Meulengracht's disease), SGPT or SGOT ≥3 higher than normal values Cardiac ejection fraction ≤ 50% GFR < 30 ml/min DLCO < 35 % or continuous oxygen dependency
Active hepatitis B or C infection or uncontrolled HIV infection
Other, active malignant disease
Prior treatment with allogeneic stem cells
Participation in a clinical trial or taking an IMP within 30 days or five times the half-life of the IMP, whichever is longer, prior to registration
Positive serum pregnancy test at screening and before first treatment or breastfeeding
PD under salvage therapy
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| Name | Affiliation | Role |
|---|---|---|
| Francis Ayuk, Prof. Dr. med. | University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of Freiburg | Freiburg im Breisgau | Baden-Wurttemberg | 79106 | Germany | ||
| University Hospital Heidelberg |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39865222 | Derived | Glockner A, Schonland S, Einsele H, Kroger N. Rationale and design of the multicenter, national, randomized, open labeled phase III trial: allogeneic stem cell transplantation as a potential curative treatment for patients with relapsed or progressed multiple myeloma (AlloRelapseMM Study). BMC Cancer. 2025 Jan 27;25(1):147. doi: 10.1186/s12885-025-13503-7. |
| Label | URL |
|---|---|
| Related Info | View source |
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| carfilzomib/lenalidomide/dexamethasone (KRD) |
| Drug |
triple regimen for first relapse should be applied according to latest Summary of Product Characteristics (SmPC) version |
|
| elotuzumab/lenalidomide/dexamethasone (ERD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| daratumumab/bortezomib/dexamethasone (DVD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| daratumumab/lenalidomide/dexamethasone (DRD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| ixazomib/lenalidomide/dexamethasone (IRD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| pomalidomide/bortezomib/dexamethasone (PVD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| carfilzomib/daratumumab/dexamethasone (KDD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| Autologous Stem Cells | Drug | Autologous Stem Cell Transplantation |
|
| daratumumab/pomalidomide/dexamethasone (DPD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| isatuximab/carfilzomib/dexamethasone (Isa-KD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| selinexor/bortezomib/dexamethasone (SVD) | Drug | triple regimen for first relapse should be applied according to latest SmPC version |
|
| Event-free survival at 3 years after randomization | A further secondary objective is to show an improvement of progress free survival and relapse free survival after allogeneic stem cell transplantation compared to conventional therapy. Events are defined as:
| from randomization to 3 years after randomization |
| Event-free survival at 5 years after randomization | A secondary objective is to show an improvement of progress free survival and relapse free survival after allogeneic stem cell transplantation compared to conventional therapy. Events are defined as:
| from randomization to 5 years after randomization |
| Change from baseline in total EORTC score at 1 year after randomization | The aim of the quality of life questionnaires (QLQ) is to provide a comparison between the two treatment arms. Quality of life according EORTC (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) & Quality of Life Questionnaire - Multiple Myeloma Module (EORTC QLQ-MY20)) will be assessed in both groups.. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology/ sickness. Patients will be observed from baseline until database lock for final analysis and adjusted mean calculated at 1 year after randomization. | at visit Screening, at the end of cycle 3 (84 days, each cycle is 28 days) of salvage therapy, 6 months and 12 months after randomization |
| Change from baseline in total EORTC score at 3 years after randomization | The aim of the quality of life questionnaires (QLQ) is to provide a comparison between the two treatment arms. Quality of life according EORTC (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) & Quality of Life Questionnaire - Multiple Myeloma Module (EORTC QLQ-MY20)) will be assessed in both groups. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology/ sickness. Patients will be observed from baseline until database lock for final analysis and adjusted mean calculated at 3 years after randomization. | at visit Screening, at the end of cycle 3 (84 days, each cycle is 28 days) of salvage therapy, 6 months, 1 year, 2 years and 3 years after randomization |
| Change from baseline in total EORTC score at 5 years after randomization | The aim of the quality of life questionnaires (QLQ) is to provide a comparison between the two treatment arms. Quality of life according EORTC (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) & Quality of Life Questionnaire - Multiple Myeloma Module (EORTC QLQ-MY20)) will be assessed in both groups. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology/ sickness. Patients will be observed from baseline until database lock for final analysis and adjusted mean calculated at 5 years after randomization. | at visit Screening, at the end of cycle 3 (84 days, each cycle is 28 days) of salvage therapy, 6 months, 1, 2, 3, 4 and 5 years after randomization |
| Time to first occurrence of remission after randomization | Patients will be followed from randomization until database lock for final analysis and cumulative incidence of first remission (partial or complete), at 2 years after randomization, is reported. | at 30 days, 100 days, 6 months, 1 and 2 years after randomization |
| Non-relapse mortality (NRM) at 1 year after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of death before any relapse at 1 year after randomization was reported. | from randomization to 1 year after randomization, an average of 1 year |
| Non-relapse mortality (NRM) at 3 years after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of death before any relapse at 3 years after randomization was reported. | from randomization to 3 years after randomization, an average of 3 years |
| Non-relapse mortality (NRM) at 5 years after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of death before any relapse at 5 years after randomization was reported. | from randomization to 5 years after randomization, an average of 5 years |
| Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 1 year after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any acute Graft-versus-Host Disease (GvHD, according to Przepiorka et al.) at 1 year after randomization is reported | at 30 days, 100 days, 6 months and 1 year after randomization, an average of 1 year |
| Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 3 years after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any acute GvHD (according to Przepiorka et al.) at 3 years after randomization is reported | at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months and 3 years after randomization, an average of 3 years |
| Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 5 years after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any acute GvHD (according to Przepiorka et al.) at 5 years after randomization is repoted. | at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months, 3, 4 and 5 years after randomization, an average of 5 years |
| Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 1 year after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any chronic GvHD (according to Jagasia et al.) at 1 year after randomization is reported. | at 30 days, 100 days, 6 months and 1 year after randomization, an average of 1 year |
| Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 3 years after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any chronic GvHD (according to Jagasia et al.) at 3 years after randomization is reported. | at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months and 3 years after randomization, an average of 3 years |
| Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 5 years after randomization | Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any chronic GvHD (according to Jagasia et al.) at 5 years after randomization is reported. | at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months, 3, 4 and 5 years after randomization, an average of 5 years |
| Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 1 year after randomization | The severity and/or intensity of an adverse event will be graded based upon the patient's symptoms according to the current active version of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any infectious complication with CTCAE grade 3 - 5 at 1 year after randomization is reported. | from randomization to 1 year after randomization, an average of 1 year |
| Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 3 years after randomization | The severity and/or intensity of an adverse event will be graded based upon the patient's symptoms according to the current active version of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any infectious complication with CTCAE grade 3 - 5 at 3 years after randomization is reported. | from randomization to 3 years after randomization, an average of 3 years |
| Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 5 years after randomization | The severity and/or intensity of an adverse event will be graded based upon the patient's symptoms according to the current active version of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any infectious complication with CTCAE grade 3 - 5 at 5 years after randomization is reported. | from randomization to 5 years after randomization, an average of 5 years |
| Change from baseline in total EORTC score (Summary Score) at 3 and 5 years after randomization | The aim of the quality of life questionnaires (QLQ) is to provide a comparison between the two treatment arms. Quality of life according EORTC (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) & Quality of Life Questionnaire - Multiple Myeloma Module (EORTC QLQ-MY20)) will be assessed in both groups. A high score for a functional scale represents a high/ healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology/ sickness. Patients will be observed from baseline until database lock for interim analysis and adjusted mean is calculated at 3 and 5 years after randomization. | at visit Screening,at the end of cycle 3 (84 days, each cycle is 28 days) of salvage therapy, 6 months, 1, 2, 3, 4 and 5 years after randomization, an average at 3 and 5 years after randomization |
| Non-relapse mortality at 1, 3 and 5 years after randomization | Patients will be observed from randomization until database lock for interim analysis and cumulative incidence of death before any relapse at 1, 3 and 5 years after randomization is reported | from randomization to 1, 3 and 5 years after randomization, an average of 1, 3 and 5 years |
| Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 1, 3 and 5 years after randomization | Patients will be observed from randomization until database lock for interim analysis and cumulative incidence of any acute GvHD (according to Przepiorka et al.) at 1, 3 and 5 years after randomization is reported | at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months, 3, 4 and 5 years after randomization, an average of 1, 3 and 5 years |
| Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 1, 3 and 5 years after randomization | Patients will be observed from randomization until database lock for interim analysis and cumulative incidence of any chronic GvHD (according to Jagasia et al.) at 1, 3 and 5 years after randomization is reported | at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months, 3, 4 and 5 years after randomization, an average of 1, 3 and 5 years |
| Time to first occurrence of Minimal Residual Disease (MRD) | Patient observed from randomization until database lock for interim analysis and until database lock for final and rate of occurrence calculated at 6 months, 1 year and 2 years after randomization | at 30 days, 100 days, 6 months, 1 and 2 years after randomization, rate of occurence at 6 months, 1 and 2 years after randomization |
| Time to first occurrence of progression | Patients will be observed from randomization until database lock for interim analysis and rates at 3 and 5 years after randomization are calculated; and patients will be observed from randomization until database lock for final analysis and rates at 1, 3, and 5 years after randomization are calculated | from randomization to 1, 3, and 5 years after randomization |
| Time to first recurrence of relapse | Patients will be followed from randomization to database lock for interim analysis and rates at 3 and 5 years after randomization are calculated; and patients will be followed from randomization to database lock for final analysis and rates at 1, 3, and 5 years after randomization are calculated. | at 1, 3, and 5 years after randomization |
| Time to first occurrence of graft failure after stem cell transplatation | Patients are followed from randomization until database lock for interim analysis and rates at 3 and 5 years post-randomization are calculated; and patients are followed from randomization until database lock for final analysis and rates at 1, 3, and 5 years post-randomization are calculated. A graft failure is defined as no stable neutrophil count > 0.5 x 10^9/l at day 28 post-SCT. | at day 30 after after randomization |
| Heidelberg |
| Baden-Wurttemberg |
| 69120 |
| Germany |
| Robert-Bosch Hospital Stuttgart | Stuttgart | Baden-Wurttemberg | 70376 | Germany |
| University Hospital Tübingen | Tübingen | Baden-Wurttemberg | 72076 | Germany |
| University Hospital of Ulm | Ulm | Baden-Wurttemberg | 89081 | Germany |
| University Hospital Augsburg | Augsburg | Bavaria | 86156 | Germany |
| University Hospital Munich ( LMU) | München | Bavaria | 80336 | Germany |
| University Hospital of the Technical University Munich rechts der Isar | München | Bavaria | 81675 | Germany |
| Hospital North Nürnberg | Nuremberg | Bavaria | 90419 | Germany |
| University Hospital Regensburg | Regensburg | Bavaria | 93053 | Germany |
| University Hospital of Würzburg | Würzburg | Bavaria | 97070 | Germany |
| Asklepios Hospital Hamburg St. Georg | Hamburg | Free and Hanseatic City of Hamburg | 20099 | Germany |
| University Medical Center Hamburg-Eppendorf | Hamburg | Free and Hanseatic City of Hamburg | 20246 | Germany |
| University Hospital Frankfurt/ Main | Frankfurt am Main | Hesse | 60590 | Germany |
| Philipps University Marburg | Marburg | Hesse | 35037 | Germany |
| University Medical Center Göttingen | Göttingen | Lower Saxony | 37075 | Germany |
| University Hospital RWTH Aachen | Aachen | North Rhine-Westphalia | 52074 | Germany |
| University Hospital Bonn | Bonn | North Rhine-Westphalia | 53127 | Germany |
| University Hospital Düsseldorf | Düsseldorf | North Rhine-Westphalia | 40225 | Germany |
| University Hospital Essen | Essen | North Rhine-Westphalia | 45147 | Germany |
| University Hospital Münster | Münster | North Rhine-Westphalia | 48149 | Germany |
| Hospital Oldenburg (AöR) | Oldenburg | Oldenburg | 26133 | Germany |
| University Medical Center Mainz | Mainz | Rhineland-Palatinate | 55131 | Germany |
| Hospital of Chemnitz gGmbH | Chemnitz | Saxony | 09116 | Germany |
| University Hospital Carl Gustav Carus | Dresden | Saxony | 01307 | Germany |
| University Hospital Halle (Saale) | Halle | Saxony-Anhalt | 06120 | Germany |
| University Hospital of Schleswig-Holstein (Campus Kiel) | Kiel | Schleswig-Holstein | 24105 | Germany |
| Charité - University of Medicine Berlin | Berlin | State of Berlin | 10117 | Germany |
| Helios Hospital Berlin-Buch | Berlin | State of Berlin | 13125 | Germany |
| University Hospital Jena | Jena | Thuringia | 07743 | Germany |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C524865 | carfilzomib |
| C546027 | elotuzumab |
| C556306 | daratumumab |
| C548400 | ixazomib |
| C467566 | pomalidomide |
| C000599209 | isatuximab |
| C585161 | selinexor |
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