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

NCT05675319 | Terminated Phase 3 DMC

• 1 other identifier: AlloRelapseMMStudy
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 30

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.

Conditions

Multiple Myeloma

Keywords

first relapse/progression after first-line therapy; allogeneic stem cell transplantation; salvage therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (19)

• Event-free survival at 1 year after randomization

  from randomization to 1 year after randomization

• Event-free survival at 3 years after randomization

  from randomization to 3 years after randomization

• Event-free survival at 5 years after randomization

  from randomization to 5 years after randomization

• Change from baseline in total EORTC score 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

  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

Other Outcomes (9)

• Event-free survival at 3 and 5 years after randomization

  from randomization to 3 and 5 years after randomization

• Change from baseline in total EORTC score (Summary Score) 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

  from randomization to 1, 3 and 5 years after randomization, an average of 1, 3 and 5 years

Study Arms (2)

Arm A (allo SCT)

EXPERIMENTAL

Allogeneic stem cell transplantation

Drug: Allogeneic Stem Cells

Arm B (conventional therapy)

ACTIVE COMPARATOR

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) or * daratumumab/pomalidomide/dexamethasone (DPD) or * isatuximab/carfilzomib/dexamethasone (Isa-KD) or * selinexor/bortezomib/dexamethasone (SVD) Alternatively, autologous stem cell transplantation may also be performed, if sufficient stem cells are still cryopreserved.

Drug: carfilzomib/lenalidomide/dexamethasone (KRD); Drug: elotuzumab/lenalidomide/dexamethasone (ERD); Drug: daratumumab/bortezomib/dexamethasone (DVD); Drug: daratumumab/lenalidomide/dexamethasone (DRD); Drug: ixazomib/lenalidomide/dexamethasone (IRD); Drug: pomalidomide/bortezomib/dexamethasone (PVD); Drug: carfilzomib/daratumumab/dexamethasone (KDD); Drug: Autologous Stem Cells; Drug: daratumumab/pomalidomide/dexamethasone (DPD); Drug: isatuximab/carfilzomib/dexamethasone (Isa-KD); Drug: selinexor/bortezomib/dexamethasone (SVD)

Interventions

Allogeneic Stem Cells DRUG

Allogeneic Stem Cell Transplantation

Arm A (allo SCT)

carfilzomib/lenalidomide/dexamethasone (KRD) DRUG

triple regimen for first relapse should be applied according to latest Summary of Product Characteristics (SmPC) version

Arm B (conventional therapy)

elotuzumab/lenalidomide/dexamethasone (ERD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

daratumumab/bortezomib/dexamethasone (DVD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

daratumumab/lenalidomide/dexamethasone (DRD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

ixazomib/lenalidomide/dexamethasone (IRD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

pomalidomide/bortezomib/dexamethasone (PVD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

carfilzomib/daratumumab/dexamethasone (KDD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

Autologous Stem Cells DRUG

Autologous Stem Cell Transplantation

Arm B (conventional therapy)

daratumumab/pomalidomide/dexamethasone (DPD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

isatuximab/carfilzomib/dexamethasone (Isa-KD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

selinexor/bortezomib/dexamethasone (SVD) DRUG

triple regimen for first relapse should be applied according to latest SmPC version

Arm B (conventional therapy)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• st 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
• Negative pregnancy test in female patients
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Staburo GmbH: collaborator
• Gemeinsamer Bundesausschuss (G-BA): collaborator
• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (30)

University Hospital of Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

University Hospital Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Robert-Bosch Hospital Stuttgart

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

University Hospital Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

University Hospital of Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

University Hospital Augsburg

Augsburg, Bavaria, 86156, Germany

Location

University Hospital Munich ( LMU)

München, Bavaria, 80336, Germany

Location

University Hospital of the Technical University Munich rechts der Isar

München, Bavaria, 81675, Germany

Location

Hospital North Nürnberg

Nuremberg, Bavaria, 90419, Germany

Location

University Hospital Regensburg

Regensburg, Bavaria, 93053, Germany

Location

University Hospital of Würzburg

Würzburg, Bavaria, 97070, Germany

Location

Asklepios Hospital Hamburg St. Georg

Hamburg, Hamburg, 20099, Germany

Location

University Medical Center Hamburg-Eppendorf

Hamburg, Hamburg, 20246, Germany

Location

University Hospital Frankfurt/ Main

Frankfurt am Main, Hesse, 60590, Germany

Location

Philipps University Marburg

Marburg, Hesse, 35037, Germany

Location

University Medical Center Göttingen

Göttingen, Lower Saxony, 37075, Germany

Location

University Hospital RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

University Hospital Bonn

Bonn, North Rhine-Westphalia, 53127, Germany

Location

University Hospital Düsseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

University Hospital Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

University Hospital Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Hospital Oldenburg (AöR)

Oldenburg, Oldenburg, 26133, Germany

Location

University Medical Center Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Hospital of Chemnitz gGmbH

Chemnitz, Saxony, 09116, Germany

Location

University Hospital Carl Gustav Carus

Dresden, Saxony, 01307, Germany

Location

University Hospital Halle (Saale)

Halle, Saxony-Anhalt, 06120, Germany

Location

University Hospital of Schleswig-Holstein (Campus Kiel)

Kiel, Schleswig-Holstein, 24105, Germany

Location

Charité - University of Medicine Berlin

Berlin, State of Berlin, 10117, Germany

Location

Helios Hospital Berlin-Buch

Berlin, State of Berlin, 13125, Germany

Location

University Hospital Jena

Jena, Thuringia, 07743, Germany

Location

Related Publications (1)

• 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.

  PMID: 39865222 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; elotuzumab; daratumumab; ixazomib; pomalidomide; isatuximab; selinexor

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Francis Ayuk, Prof. Dr. med.

  University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2022
• First Posted: January 9, 2023
• Study Start: March 3, 2023
• Primary Completion: March 14, 2025
• Study Completion: March 21, 2025
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (30)