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Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy (AlloRelapseMM)

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Allogeneic Stem Cells
carfilzomib/lenalidomide/dexamethasone (KRD)
elotuzumab/lenalidomide/dexamethasone (ERD)
daratumumab/bortezomib/dexamethasone (DVD)
daratumumab/lenalidomide/dexamethasone (DRD)
ixazomib/lenalidomide/dexamethasone (IRD)
pomalidomide/bortezomib/dexamethasone (PVD)
carfilzomib/daratumumab/dexamethasone (KDD)
Autologous Stem Cells
Sponsored by
Universitätsklinikum Hamburg-Eppendorf
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring first relapse/progression after first-line therapy, allogeneic stem cell transplantation, salvage therapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients eligible for study inclusion must meet criteria 1- 7 at registration and all of the following criteria before randomization: Multiple Myeloma Age 18 - 65 years A signed informed consent form must be obtained before participation in the study Age 66 - 70 years, if comorbidity index according to Sorror score = 0 and ECOG ≤ 1 1st relapse/ progression according to IMWG criteria after first-line therapy (consisting of induction therapy followed by autologous transplantation once or twice and maintenance therapy), Additionally: meeting the need for treatment based on the SLiM criteria Negative pregnancy test in female patients Maximum of 1 cycle salvage therapy prior to study inclusion Availability of a fully compatible stem cell donor (HLA-ident. Sibling or 10/10 MUD or 9/10 MMUD if mismatch affects DQB) after 3 cycles salvage therapy CR/PR or SD according to IMWG-criteria after 3 cycles salvage therapy within the study 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 < 50% and/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

Sites / Locations

  • University Hospital of Freiburg
  • University Hospital Heidelberg
  • Robert-Bosch Hospital StuttgartRecruiting
  • University Hospital Tübingen
  • University Hospital of Ulm
  • University Hospital AugsburgRecruiting
  • University Hospital Munich ( LMU)
  • Munich Hospital Schwabing
  • University Hospital of the Technical University Munich rechts der Isar
  • Hospital North Nürnberg
  • University Hospital Regensburg
  • University Hospital of WürzburgRecruiting
  • University Hospital Frankfurt/ MainRecruiting
  • Philipps University MarburgRecruiting
  • University Medical Center Göttingen
  • University Hospital RWTH Aachen
  • University Hospital BonnRecruiting
  • University Hospital Düsseldorf
  • University Hospital Essen
  • University Hospital Münster
  • University Medical Center Mainz
  • University Hospital Halle (Saale)
  • Hospital of Chemnitz gGmbHRecruiting
  • University Hospital Carl Gustav CarusRecruiting
  • University Hospital of Schleswig-Holstein (Campus Kiel)
  • University Hospital JenaRecruiting
  • Charité - University of Medicine Berlin
  • Helios Hospital Berlin-BuchRecruiting
  • Asklepios Hospital Hamburg St. Georg
  • University Medical Center Hamburg-EppendorfRecruiting
  • Hospital Oldenburg (AöR)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A (allo SCT)

Arm B (conventional therapy)

Arm Description

Allogeneic stem cell transplantation

Currently approved triple regimens for first relapse: carfilzomib/lenalidomide/dexamethasone (KRD) or elotuzumab/lenalidomide/dexamethasone (ERD) or daratumumab/bortezomib/dexamethasone DVD) or daratumumab/lenalidomide/dexamethasone (DRD) or ixazomib/lenalidomide/dexamethasone (IRD) or pomalidomide/bortezomib/dexamethasone (PVD) or carfilzomib/daratumumab/dexamethasone (KDD) Alternatively, autologous stem cell transplantation may also be performed, if sufficient stem cells are still cryopreserved.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
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.
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.
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 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.
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.
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.
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.
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
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
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.
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.
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.
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 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 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 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.

Full Information

First Posted
November 6, 2022
Last Updated
April 22, 2023
Sponsor
Universitätsklinikum Hamburg-Eppendorf
Collaborators
Gemeinsamer Bundesausschuss (G-BA), Staburo GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT05675319
Brief Title
Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy
Acronym
AlloRelapseMM
Official Title
Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 3, 2023 (Actual)
Primary Completion Date
March 2028 (Anticipated)
Study Completion Date
March 2033 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitätsklinikum Hamburg-Eppendorf
Collaborators
Gemeinsamer Bundesausschuss (G-BA), Staburo GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
first relapse/progression after first-line therapy, allogeneic stem cell transplantation, salvage therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
482 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A (allo SCT)
Arm Type
Experimental
Arm Description
Allogeneic stem cell transplantation
Arm Title
Arm B (conventional therapy)
Arm Type
Active Comparator
Arm Description
Currently approved triple regimens for first relapse: carfilzomib/lenalidomide/dexamethasone (KRD) or elotuzumab/lenalidomide/dexamethasone (ERD) or daratumumab/bortezomib/dexamethasone DVD) or daratumumab/lenalidomide/dexamethasone (DRD) or ixazomib/lenalidomide/dexamethasone (IRD) or pomalidomide/bortezomib/dexamethasone (PVD) or carfilzomib/daratumumab/dexamethasone (KDD) Alternatively, autologous stem cell transplantation may also be performed, if sufficient stem cells are still cryopreserved.
Intervention Type
Drug
Intervention Name(s)
Allogeneic Stem Cells
Intervention Description
Allogeneic Stem Cell Transplantation
Intervention Type
Drug
Intervention Name(s)
carfilzomib/lenalidomide/dexamethasone (KRD)
Intervention Description
triple regimen for first relapse should be applied according to latest Summary of Product Characteristics (SmPC) version
Intervention Type
Drug
Intervention Name(s)
elotuzumab/lenalidomide/dexamethasone (ERD)
Intervention Description
triple regimen for first relapse should be applied according to latest SmPC version
Intervention Type
Drug
Intervention Name(s)
daratumumab/bortezomib/dexamethasone (DVD)
Intervention Description
triple regimen for first relapse should be applied according to latest SmPC version
Intervention Type
Drug
Intervention Name(s)
daratumumab/lenalidomide/dexamethasone (DRD)
Intervention Description
triple regimen for first relapse should be applied according to latest SmPC version
Intervention Type
Drug
Intervention Name(s)
ixazomib/lenalidomide/dexamethasone (IRD)
Intervention Description
triple regimen for first relapse should be applied according to latest SmPC version
Intervention Type
Drug
Intervention Name(s)
pomalidomide/bortezomib/dexamethasone (PVD)
Intervention Description
triple regimen for first relapse should be applied according to latest SmPC version
Intervention Type
Drug
Intervention Name(s)
carfilzomib/daratumumab/dexamethasone (KDD)
Intervention Description
triple regimen for first relapse should be applied according to latest SmPC version
Intervention Type
Drug
Intervention Name(s)
Autologous Stem Cells
Intervention Description
Autologous Stem Cell Transplantation
Primary Outcome Measure Information:
Title
Overall survival at five years after randomization
Description
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
Secondary Outcome Measure Information:
Title
Event-free survival at 1 year after randomization
Description
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
Title
Event-free survival at 3 years after randomization
Description
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
Title
Event-free survival at 5 years after randomization
Description
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
Title
Change from baseline in total EORTC score at 1 year after randomization
Description
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
Title
Change from baseline in total EORTC score at 3 years after randomization
Description
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
Title
Change from baseline in total EORTC score at 5 years after randomization
Description
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
Title
Time to first occurrence of remission after randomization
Description
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
Title
Non-relapse mortality (NRM) at 1 year after randomization
Description
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
Title
Non-relapse mortality (NRM) at 3 years after randomization
Description
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
Title
Non-relapse mortality (NRM) at 5 years after randomization
Description
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
Title
Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 1 year after randomization
Description
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
Title
Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 3 years after randomization
Description
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
Title
Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 5 years after randomization
Description
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
Title
Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 1 year after randomization
Description
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
Title
Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 3 years after randomization
Description
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
Title
Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 5 years after randomization
Description
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
Title
Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 1 year after randomization
Description
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
Title
Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 3 years after randomization
Description
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
Title
Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 5 years after randomization
Description
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
Other Pre-specified Outcome Measures:
Title
Event-free survival at 3 and 5 years after randomization
Description
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: Progression or Relapse or Engraftment Failure or Death of any cause
Time Frame
from randomization to 3 and 5 years after randomization
Title
Change from baseline in total EORTC score (Summary Score) at 3 and 5 years after randomization
Description
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.
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, an average at 3 and 5 years after randomization
Title
Non-relapse mortality at 1, 3 and 5 years after randomization
Description
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
Time Frame
from randomization to 1, 3 and 5 years after randomization, an average of 1, 3 and 5 years
Title
Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 1, 3 and 5 years after randomization
Description
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
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 1, 3 and 5 years
Title
Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 1, 3 and 5 years after randomization
Description
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
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 1, 3 and 5 years
Title
Time to first occurrence of Minimal Residual Disease (MRD)
Description
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
Time Frame
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
Title
Time to first occurrence of progression
Description
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
Time Frame
from randomization to 1, 3, and 5 years after randomization
Title
Time to first recurrence of relapse
Description
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.
Time Frame
at 1, 3, and 5 years after randomization
Title
Time to first occurrence of graft failure after stem cell transplatation
Description
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.
Time Frame
at day 30 after after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients eligible for study inclusion must meet criteria 1- 7 at registration and all of the following criteria before randomization: Multiple Myeloma Age 18 - 65 years A signed informed consent form must be obtained before participation in the study Age 66 - 70 years, if comorbidity index according to Sorror score = 0 and ECOG ≤ 1 1st relapse/ progression according to IMWG criteria after first-line therapy (consisting of induction therapy followed by autologous transplantation once or twice and maintenance therapy), Additionally: meeting the need for treatment based on the SLiM criteria Negative pregnancy test in female patients Maximum of 1 cycle salvage therapy prior to study inclusion Availability of a fully compatible stem cell donor (HLA-ident. Sibling or 10/10 MUD or 9/10 MMUD if mismatch affects DQB) after 3 cycles salvage therapy CR/PR or SD according to IMWG-criteria after 3 cycles salvage therapy within the study 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 < 50% and/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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicolaus Kröger, Prof. Dr.
Phone
+4940741054851
Email
n.kroeger@uke.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolaus Kröger, Prof. Dr.
Organizational Affiliation
University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Freiburg
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ralph Wäsch, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Ralph Wäsch, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Monika Engelhardt, Prof. Dr.
Facility Name
University Hospital Heidelberg
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan Schönland, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Stefan Schönland, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Ute Hegenbart, Prof. Dr.
Facility Name
Robert-Bosch Hospital Stuttgart
City
Stuttgart
State/Province
Baden-Württemberg
ZIP/Postal Code
70376
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Kaufmann, Dr.
First Name & Middle Initial & Last Name & Degree
Martin Kaufmann, Dr.
First Name & Middle Initial & Last Name & Degree
Sonja Martin, Dr.
Facility Name
University Hospital Tübingen
City
Tübingen
State/Province
Baden-Württemberg
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wolfgang Bethge, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Wolfgang Bethge, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Christoph Faul, Dr.
First Name & Middle Initial & Last Name & Degree
Britta Besemer, Dr.
Facility Name
University Hospital of Ulm
City
Ulm
State/Province
Baden-Württemberg
ZIP/Postal Code
89081
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisa Sala, Dr.
First Name & Middle Initial & Last Name & Degree
Elisa Sala, Dr.
First Name & Middle Initial & Last Name & Degree
Miriam Knull, Dr.
Facility Name
University Hospital Augsburg
City
Augsburg
State/Province
Bayern
ZIP/Postal Code
86156
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christoph Schmid, Pof. Dr.
First Name & Middle Initial & Last Name & Degree
Christoph Schmid, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Tim Pfeiffer, Dr.
Facility Name
University Hospital Munich ( LMU)
City
München
State/Province
Bayern
ZIP/Postal Code
80336
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johanna Tischer, PD Dr.
First Name & Middle Initial & Last Name & Degree
Johanna Tischer, PD Dr.
First Name & Middle Initial & Last Name & Degree
Sebastian Theurich, Prof. Dr.
Facility Name
Munich Hospital Schwabing
City
München
State/Province
Bayern
ZIP/Postal Code
80804
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Hausmann, Dr.
First Name & Middle Initial & Last Name & Degree
Andreas Hausmann, Dr.
First Name & Middle Initial & Last Name & Degree
Nadine Anstötz, Dr.
Facility Name
University Hospital of the Technical University Munich rechts der Isar
City
München
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mareike Verbeek, Dr.
First Name & Middle Initial & Last Name & Degree
Mareike Verbeek, Dr.
First Name & Middle Initial & Last Name & Degree
Peter Herhaus, Dr.
Facility Name
Hospital North Nürnberg
City
Nürnberg
State/Province
Bayern
ZIP/Postal Code
90419
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kerstin Schäfer-Eckart, Dr.
First Name & Middle Initial & Last Name & Degree
Kerstin Schäfer-Eckart, Dr.
First Name & Middle Initial & Last Name & Degree
Knut Wendelin, Dr.
Facility Name
University Hospital Regensburg
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93053
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthias Edinger, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Matthias Edinger, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Daniel Wolff, Prof. Dr.
Facility Name
University Hospital of Würzburg
City
Würzburg
State/Province
Bayern
ZIP/Postal Code
97070
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sabrina Kraus, Dr.
First Name & Middle Initial & Last Name & Degree
Sabrina Kraus, Dr.
First Name & Middle Initial & Last Name & Degree
Jochen Frietsch, Dr.
Facility Name
University Hospital Frankfurt/ Main
City
Frankfurt am Main
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ivana von Metzler, Dr.
First Name & Middle Initial & Last Name & Degree
Ivana von Metzler, Dr.
First Name & Middle Initial & Last Name & Degree
Fabian Lang, Dr.
Facility Name
Philipps University Marburg
City
Marburg
State/Province
Hessen
ZIP/Postal Code
35037
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Burchert, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Andreas Burchert, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Kristina Sohlbach, Dr.
Facility Name
University Medical Center Göttingen
City
Göttingen
State/Province
Niedersachsen
ZIP/Postal Code
37075
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wolfram Jung, Dr.
First Name & Middle Initial & Last Name & Degree
Wolfram Jung, Dr.
First Name & Middle Initial & Last Name & Degree
Justin Hasenkamp, Dr.
Facility Name
University Hospital RWTH Aachen
City
Aachen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
52074
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edgar Jost, PD Dr.
First Name & Middle Initial & Last Name & Degree
Edgar Jost, PD Dr.
First Name & Middle Initial & Last Name & Degree
Deniz Gezer, Dr.
Facility Name
University Hospital Bonn
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53127
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Holderried, Dr.
First Name & Middle Initial & Last Name & Degree
Tobias Holderried, Dr.
First Name & Middle Initial & Last Name & Degree
Martin Schumacher, Dr.
Facility Name
University Hospital Düsseldorf
City
Düsseldorf
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guido Kobbe, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Guido Kobbe, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Roland Fenk, Prof. Dr.
Facility Name
University Hospital Essen
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rudolf Trenschel, Dr.
First Name & Middle Initial & Last Name & Degree
Rudolf Trenschel, Dr.
First Name & Middle Initial & Last Name & Degree
Thomas Schroeder, PD Dr.
Facility Name
University Hospital Münster
City
Münster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthias Stelljes, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Matthias Stelljes, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Evgenii Shumilov, Dr.
Facility Name
University Medical Center Mainz
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Maria Wagner-Drouet, Dr.
First Name & Middle Initial & Last Name & Degree
Eva Maria Wagner-Douret, Dr.
First Name & Middle Initial & Last Name & Degree
Markus Munder, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Beate Hauptrock, Dr.
Facility Name
University Hospital Halle (Saale)
City
Halle (Saale)
State/Province
Sachsen-Anhalt
ZIP/Postal Code
06120
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lutz Müller, PD Dr.
First Name & Middle Initial & Last Name & Degree
Lutz Müller, PD Dr.
First Name & Middle Initial & Last Name & Degree
Thomas Weber, Dr.
Facility Name
Hospital of Chemnitz gGmbH
City
Chemnitz
State/Province
Sachsen
ZIP/Postal Code
09116
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mathias Hänel, PD Dr.
First Name & Middle Initial & Last Name & Degree
Mathias Hänel, PD Dr.
First Name & Middle Initial & Last Name & Degree
Anke Morgner, Dr.
Facility Name
University Hospital Carl Gustav Carus
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raphael Teipel, Dr.
First Name & Middle Initial & Last Name & Degree
Raphael Teipel, Dr.
First Name & Middle Initial & Last Name & Degree
Karolin Trautmann-Grill, Dr.
Facility Name
University Hospital of Schleswig-Holstein (Campus Kiel)
City
Kiel
State/Province
Schleswig-Holstein
ZIP/Postal Code
24105
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalie Schub, Dr.
First Name & Middle Initial & Last Name & Degree
Natalie Schub, Dr.
First Name & Middle Initial & Last Name & Degree
Lars Fransecky, Dr.
Facility Name
University Hospital Jena
City
Jena
State/Province
Thüringen
ZIP/Postal Code
07743
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Inken Hilgendorf, PD Dr.
First Name & Middle Initial & Last Name & Degree
Inken Hilgendorf, PD Dr.
First Name & Middle Initial & Last Name & Degree
Wibke Göpel, Dr.
Facility Name
Charité - University of Medicine Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Igor-Wolfgang Blau, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Igor-Wolfgang Blau, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Giang Lam Vuong, Dr.
Facility Name
Helios Hospital Berlin-Buch
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Judith Niederland, Dr.
First Name & Middle Initial & Last Name & Degree
Judith Niederland, Dr.
First Name & Middle Initial & Last Name & Degree
Pearl van Heteren, Dr.
Facility Name
Asklepios Hospital Hamburg St. Georg
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ahmet Elmaagacli, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Ahmet Elmaagacli, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Hans Salwender, Dr.
Facility Name
University Medical Center Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolaus Kröger, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Nicolaus Kröger, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Christine Wolschke, Dr.
Facility Name
Hospital Oldenburg (AöR)
City
Oldenburg
ZIP/Postal Code
26133
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christoph Kimmich, Dr.
First Name & Middle Initial & Last Name & Degree
Christoph Kimmich, Dr.
First Name & Middle Initial & Last Name & Degree
Jochen Casper, Prof. Dr.

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy

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