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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Allogeneic Stem Cell Transplantation
triple regimen for first relapse should be applied according to latest Summary of Product Characteristics (SmPC) version
triple regimen for first relapse should be applied according to latest SmPC version
triple regimen for first relapse should be applied according to latest SmPC version
triple regimen for first relapse should be applied according to latest SmPC version
triple regimen for first relapse should be applied according to latest SmPC version
triple regimen for first relapse should be applied according to latest SmPC version
triple regimen for first relapse should be applied according to latest SmPC version
Autologous Stem Cell Transplantation
triple regimen for first relapse should be applied according to latest SmPC version
triple regimen for first relapse should be applied according to latest SmPC version
triple regimen for first relapse should be applied according to latest SmPC version
University Hospital of Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, Germany
University Hospital Heidelberg
Heidelberg, Baden-Wurttemberg, Germany
Robert-Bosch Hospital Stuttgart
Stuttgart, Baden-Wurttemberg, Germany
University Hospital Tübingen
Tübingen, Baden-Wurttemberg, Germany
University Hospital of Ulm
Ulm, Baden-Wurttemberg, Germany
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.
Time frame: at 5 years after randomization
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: * Progression or * Relapse or * Engraftment Failure or * Death of any cause
Time frame: from randomization to 1 year after randomization
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: * Progression or * Relapse or * Engraftment Failure or * Death of any cause
Time frame: 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: * Progression or * Relapse or * Engraftment Failure or * Death of any cause
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: from randomization to 5 years after randomization, an average of 5 years
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