Clinical trial NCT05675319: Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy
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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: first relapse/progression after first-line therapy
allogeneic stem cell transplantation
salvage therapy
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Gemeinsamer Bundesausschuss (G-BA)
name: Staburo GmbH
First posted: 2023-01-09
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall survival at five years after randomization
timeFrame: at 5 years after randomization
Secondary outcomes:
measure: Event-free survival at 1 year after randomization
timeFrame: from randomization to 1 year after randomization
measure: Event-free survival at 3 years after randomization
timeFrame: from randomization to 3 years after randomization
measure: Event-free survival at 5 years after randomization
timeFrame: from randomization to 5 years after randomization
measure: Change from baseline in total EORTC score at 1 year after randomization
timeFrame: 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
measure: Change from baseline in total EORTC score at 3 years after randomization
timeFrame: 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
measure: Change from baseline in total EORTC score at 5 years after randomization
timeFrame: 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
measure: Time to first occurrence of remission after randomization
timeFrame: at 30 days, 100 days, 6 months, 1 and 2 years after randomization
measure: Non-relapse mortality (NRM) at 1 year after randomization
timeFrame: from randomization to 1 year after randomization, an average of 1 year
measure: Non-relapse mortality (NRM) at 3 years after randomization
timeFrame: from randomization to 3 years after randomization, an average of 3 years
measure: Non-relapse mortality (NRM) at 5 years after randomization
timeFrame: from randomization to 5 years after randomization, an average of 5 years
measure: Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 1 year after randomization
timeFrame: at 30 days, 100 days, 6 months and 1 year after randomization, an average of 1 year
measure: Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 3 years after randomization
timeFrame: 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
measure: Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 5 years after randomization
timeFrame: 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
measure: Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 1 year after randomization
timeFrame: at 30 days, 100 days, 6 months and 1 year after randomization, an average of 1 year
measure: Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 3 years after randomization
timeFrame: 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
measure: Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 5 years after randomization
timeFrame: 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
measure: Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 1 year after randomization
timeFrame: from randomization to 1 year after randomization, an average of 1 year
measure: Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 3 years after randomization
timeFrame: from randomization to 3 years after randomization, an average of 3 years
measure: Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 5 years after randomization
timeFrame: from randomization to 5 years after randomization, an average of 5 years
Other outcomes:
measure: Event-free survival at 3 and 5 years after randomization
timeFrame: from randomization to 3 and 5 years after randomization
measure: Change from baseline in total EORTC score (Summary Score) at 3 and 5 years after randomization
timeFrame: 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
measure: Non-relapse mortality at 1, 3 and 5 years after randomization
timeFrame: from randomization to 1, 3 and 5 years after randomization, an average of 1, 3 and 5 years
measure: Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 1, 3 and 5 years after randomization
timeFrame: 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
measure: Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 1, 3 and 5 years after randomization
timeFrame: 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
measure: Time to first occurrence of Minimal Residual Disease (MRD)
timeFrame: 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
measure: Time to first occurrence of progression
timeFrame: from randomization to 1, 3, and 5 years after randomization
measure: Time to first recurrence of relapse
timeFrame: at 1, 3, and 5 years after randomization
measure: Time to first occurrence of graft failure after stem cell transplatation
timeFrame: at day 30 after after randomization
Locations:
city: Freiburg
country: Germany
facility: University Hospital of Freiburg
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
state: Baden-Württemberg
city: Stuttgart
country: Germany
facility: Robert-Bosch Hospital Stuttgart
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: University Hospital Tübingen
state: Baden-Württemberg
city: Ulm
country: Germany
facility: University Hospital of Ulm
state: Baden-Württemberg
city: Augsburg
country: Germany
facility: University Hospital Augsburg
state: Bayern
city: München
country: Germany
facility: University Hospital Munich ( LMU)
state: Bayern
city: München
country: Germany
facility: University Hospital of the Technical University Munich rechts der Isar
state: Bayern
city: Nürnberg
country: Germany
facility: Hospital North Nürnberg
state: Bayern
city: Regensburg
country: Germany
facility: University Hospital Regensburg
state: Bayern
city: Würzburg
country: Germany
facility: University Hospital of Würzburg
state: Bayern
city: Frankfurt am Main
country: Germany
facility: University Hospital Frankfurt/ Main
state: Hessen
city: Marburg
country: Germany
facility: Philipps University Marburg
state: Hessen
city: Göttingen
country: Germany
facility: University Medical Center Göttingen
state: Niedersachsen
city: Aachen
country: Germany
facility: University Hospital RWTH Aachen
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: University Hospital Bonn
state: Nordrhein-Westfalen
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: University Hospital Essen
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: University Hospital Münster
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: University Medical Center Mainz
state: Rheinland-Pfalz
city: Halle (Saale)
country: Germany
facility: University Hospital Halle (Saale)
state: Sachsen-Anhalt
city: Chemnitz
country: Germany
facility: Hospital of Chemnitz gGmbH
state: Sachsen
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
state: Sachsen
city: Kiel
country: Germany
facility: University Hospital of Schleswig-Holstein (Campus Kiel)
state: Schleswig-Holstein
city: Jena
country: Germany
facility: University Hospital Jena
state: Thüringen
city: Berlin
country: Germany
facility: Charité - University of Medicine Berlin
city: Berlin
country: Germany
facility: Helios Hospital Berlin-Buch
city: Hamburg
country: Germany
facility: Asklepios Hospital Hamburg St. Georg
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Oldenburg
country: Germany
facility: Hospital Oldenburg (AöR)
Study officials:
affiliation: University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation
name: Nicolaus Kröger, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: