Overview
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.
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