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Phase II Trial for Newly Diagnosed Low-risk Multiple Myeloma Patients Comparing 6 Cycles of Isatuximab With Lenalidomide/Bortezomib/Dexamethasone (I-VRD) Compared to 3 Cycles of I-VRD Followed by One Cycle of High-dose Therapy and Both Arms Followed by Maintenance Therapy With I-R. (ELIAS)
Multiple myeloma (MM) is a malignant disease of the BM characterized by clonal expansion of plasma cells. Current guidelines recommend that newly diagnosed transplant-eligible patients with multiple myeloma (NDMMTE) shall undergo several cycles of induction, followed by one or two cycles high-dose melphalan followed by autologous stem cell transfusion (ASCT). Currently, induction therapy schemes usually consist of an immunomodulator (thalidomide or lenalidomide), a transmembrane glycoprotein CD38 targeting antibody, a proteasome inhibitor, and dexamethasone. The induction therapy is then followed by stem cell mobilization and subsequently one or two cycles of high-dose melphalan-chemotherapy based on the initial cytogenetic findings of the malignant plasma cells and the initial stage of the disease. Essentially, all NDMMTE patients undergo at least one cycle of high-dose chemotherapy, which is associated with high morbidity including acute toxicities like cytopenia, infection, and long-term effects such as myelodysplastic disease (MDS) and secondary malignancies and rarely death. Based on preliminary data and published reports, exposure to high-doses of the genotoxic agent melphalan might render the residual malignant myeloma cells into more aggressive clones, accelerating relapse by potentially altering stroma. Finally, exposure to melphalan is well known to increase the possibility of secondary malignant disease development. In MM patients, high-dose melphalan therapy improves OS and PFS if patients from all risk groups are taken in consideration. Yet, it remains to be answered, whether also low risk patients have an additional benefit from high-dose melphalan therapy or whether for these patients, a less toxic regime would be similarly sufficient with regard to PFS and OS. The challenging question will be whether the effect of melphalan on initial disease control might be outpaced by the negative effects as described above. Hence, the sponsor will explore whether treatment with high-dose melphalan might represent an overtreatment for certain subpopulation myeloma patients. These patients might be adequately treated without need of high-dose melphalan as part of the first line treatment. The sponsor, therefore, proposes to use a personalized approach to evaluate whether patients with a low-risk profile and with a gene expression profile indicating a standard risk of relapse might be sufficiently treated with an intensified induction course without subsequent upfront high-dose melphalan chemotherapy.
Details
| Lead sponsor | University Hopsital Schleswig Holstein Campus Lübeck |
|---|---|
| Phase | Phase 2/Phase 3 |
| Status | RECRUITING |
| Enrolment | 100 |
| Start date | 2023-02-03 |
| Completion | 2028-10 |
Conditions
- Newly Diagnosed Multiple Myeloma
Interventions
- Isatuximab
- Lenalidomide
- Bortezomib
- Dexamethasone
- autologous stem cell transplant
Primary outcomes
- Rate of minimal residual negativity combined with complete remission rate according to IMWG and EuroFlow criteria — Week 40 after start of induction therapy (18 weeks after randomization).
Minimal Residual Disease (MRD) (less than 1 malignant plasma cell per 1 Mio bone marrow cells based on EuroFLow criteria) and complete remission rate (no paraprotein detectable, Immunfixation negative urine and serum) according to international myeloma working group (IMWG) criteria after high dose chemotherapy or 6 courses of IVRD (Isatuximab, Bortezomib, lenalidomide, Dexamethasone) (week 40)
Countries
Germany