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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 70 Years
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05675319
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Universitätsklinikum Hamburg-Eppendorf
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Nicolaus Kröger, Prof. Dr.
Principal Investigator Affiliation	University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Germany
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Multiple Myeloma

Additional Details

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.

Arms & Interventions

Arms

Experimental: Arm A (allo SCT)

Allogeneic stem cell transplantation

Active Comparator: Arm B (conventional therapy)

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.

Interventions

Drug: - Allogeneic Stem Cells

Allogeneic Stem Cell Transplantation

Drug: - carfilzomib/lenalidomide/dexamethasone (KRD)

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

Drug: - elotuzumab/lenalidomide/dexamethasone (ERD)