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

Multiple Myeloma Clinical Trial

— AlloRelapseMM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05675319
• Other study ID #: AlloRelapseMMStudy
• Status: Recruiting
• Phase: Phase 3
• Start date: March 3, 2023
• Est. completion date: March 2033

Study information

• Verified date: April 2024
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: Nicolaus Kröger, Prof. Dr.
• Phone: +4940741054851
• Email: n.kroeger[@]uke.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 482
• Est. completion date: March 2033
• Est. primary completion date: March 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

Patients eligible for study inclusion must meet criteria 1- 7 at registration and all of the following criteria before randomization:

1. Multiple Myeloma

2. Age 18 - 65 years

3. A signed informed consent form must be obtained before participation in the study

4. Age 66 - 70 years, if comorbidity index according to Sorror score = 0 and ECOG = 1

5. 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-CRAB-criteria

6. Negative pregnancy test in female patients

7. Maximum of 1 cycle salvage therapy prior to study inclusion

8. 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

9. 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:

1. 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

2. Active hepatitis B or C infection or uncontrolled HIV infection

3. Other, active malignant disease

4. Prior treatment with allogeneic stem cells

5. 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

6. Positive serum pregnancy test at screening and before first treatment or breastfeeding

7. PD under salvage therapy

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Allogeneic Stem Cells
Allogeneic Stem Cell Transplantation
• carfilzomib/lenalidomide/dexamethasone (KRD)
triple regimen for first relapse should be applied according to latest Summary of Product Characteristics (SmPC) version
• elotuzumab/lenalidomide/dexamethasone (ERD)
triple regimen for first relapse should be applied according to latest SmPC version
• daratumumab/bortezomib/dexamethasone (DVD)
triple regimen for first relapse should be applied according to latest SmPC version
• daratumumab/lenalidomide/dexamethasone (DRD)
triple regimen for first relapse should be applied according to latest SmPC version
• ixazomib/lenalidomide/dexamethasone (IRD)
triple regimen for first relapse should be applied according to latest SmPC version
• pomalidomide/bortezomib/dexamethasone (PVD)
triple regimen for first relapse should be applied according to latest SmPC version
• carfilzomib/daratumumab/dexamethasone (KDD)
triple regimen for first relapse should be applied according to latest SmPC version
• Autologous Stem Cells
Autologous Stem Cell Transplantation
• daratumumab/pomalidomide/dexamethasone (DPD)
triple regimen for first relapse should be applied according to latest SmPC version
• isatuximab/carfilzomib/dexamethasone (Isa-KD)
triple regimen for first relapse should be applied according to latest SmPC version
• selinexor/bortezomib/dexamethasone (SVD)
triple regimen for first relapse should be applied according to latest SmPC version

Locations

Country	Name	City	State
Germany	University Hospital RWTH Aachen	Aachen	Nordrhein-Westfalen
Germany	University Hospital Augsburg	Augsburg	Bayern
Germany	Charité - University of Medicine Berlin	Berlin
Germany	Helios Hospital Berlin-Buch	Berlin
Germany	University Hospital Bonn	Bonn	Nordrhein-Westfalen
Germany	Hospital of Chemnitz gGmbH	Chemnitz	Sachsen
Germany	University Hospital Carl Gustav Carus	Dresden	Sachsen
Germany	University Hospital Düsseldorf	Düsseldorf	Nordrhein-Westfalen
Germany	University Hospital Essen	Essen	Nordrhein-Westfalen
Germany	University Hospital Frankfurt/ Main	Frankfurt am Main	Hessen
Germany	University Hospital of Freiburg	Freiburg	Baden-Württemberg
Germany	University Medical Center Göttingen	Göttingen	Niedersachsen
Germany	University Hospital Halle (Saale)	Halle (Saale)	Sachsen-Anhalt
Germany	Asklepios Hospital Hamburg St. Georg	Hamburg
Germany	University Medical Center Hamburg-Eppendorf	Hamburg
Germany	University Hospital Heidelberg	Heidelberg	Baden-Württemberg
Germany	University Hospital Jena	Jena	Thüringen
Germany	University Hospital of Schleswig-Holstein (Campus Kiel)	Kiel	Schleswig-Holstein
Germany	University Medical Center Mainz	Mainz	Rheinland-Pfalz
Germany	Philipps University Marburg	Marburg	Hessen
Germany	Munich Hospital Schwabing	München	Bayern
Germany	University Hospital Munich ( LMU)	München	Bayern
Germany	University Hospital of the Technical University Munich rechts der Isar	München	Bayern
Germany	University Hospital Münster	Münster	Nordrhein-Westfalen
Germany	Hospital North Nürnberg	Nürnberg	Bayern
Germany	Hospital Oldenburg (AöR)	Oldenburg
Germany	University Hospital Regensburg	Regensburg	Bayern
Germany	Robert-Bosch Hospital Stuttgart	Stuttgart	Baden-Württemberg
Germany	University Hospital Tübingen	Tübingen	Baden-Württemberg
Germany	University Hospital of Ulm	Ulm	Baden-Württemberg
Germany	University Hospital of Würzburg	Würzburg	Bayern

Sponsors (3)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Gemeinsamer Bundesausschuss (G-BA), Staburo GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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: Progression or; Relapse or; Engraftment Failure or; Death of any cause	from randomization to 3 and 5 years after randomization
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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
Secondary	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	from randomization to 1 year after randomization
Secondary	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	from randomization to 3 years after randomization
Secondary	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	from randomization to 5 years after randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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