Elotuzumab in Patients With Multiple Myeloma Before and After Peripheral Stem Cell Autologous Graft (IFM2016-03)
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|ClinicalTrials.gov Identifier: NCT03393273|
Recruitment Status : Not yet recruiting
First Posted : January 8, 2018
Last Update Posted : January 8, 2018
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Elotuzumab||Phase 2|
In patients of 65 years of age or older, intensive treatment (TI) with hematopoietic stem cell autologous graft (ASCH) is not considered as the gold standard. Nowadays, given the rise of new treatments, new studies assessing TI with ASCH in elderly, seem required. The association bortezomib (VEL) - thalidomide (THAL) - dexamethasone (DEX) is considered as the standard induction (Kumar, Flinn et al. 2012, Ludwig, Viterbo et al. 2013). However, more and more strategies with immunotherapies are developed. Furthermore, it looks encouraging to use several monoclonal antibodies at different clinical development levels. Thus, elotuzumab (ELO) is an IgG1 (immunoglobulin gamma-1) (IgGκ) humanized monoclonal antibody directed against SLAMF7. SLAMF7 is a glycoprotein expressed by myeloma cells and natural killer (NK) but not by healthy tissues. Consequently, elotuzumab can kill specifically myeloma cells without affecting healthy tissues (Hsi, Steinle et al. 2008). A phase I study assessed the safety of ELO in association with VEL, REV (Lenalidomide) and DEX in induction first-line treatment in elderly patients with median age of 67 years (Usmani, Sexton et al. 2015). There were no significant increase of side effects with this association compared with side effects usually reported with VEL, REV and DEX. Thus, adding ELO could lead to an increase of response rate, with no increase of toxicity.
For more than 10 years, the standard intensive treatment associates a MEL (MELPHALAN) conditioning (200 mg/m2) with a blood graft. In a recent study, almost all patients aged between 65-69 and 70-74 years received MEL at 200 mg/m2. The adverse events rate was similar between the different ages and a very low non-tied relapse mortality. Thus, in elderly patients selected, the use of MEL at 200 mg/m2 seems sure.
Moreover, it's widely admitted that the conditioning treatment should be based on an efficient drugs association with a limited toxicity. Studies assessing consolidation treatment with an association of new drugs are limited. Initial results suggest that the use of new drugs after intensive treatment (IT) with ASCH should increase response rate and improve progression-free survival and global survival.
The aim of this study IFM 2016-03 is to assess IT with AHSCT (Autologous hematopoietic stem cell transplantation) in elderly and to associate the different steps (induction, high dose conditioning, consolidation) with immunotherapy. Given the prior results of IFM and international studies, a VGPR (Very Good Partial Response) rate of around 85% is expected.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Induction and Consolidation With Elotuzumab Before and After Peripheral Stem Cell Autologous Graft in Elderly Patients With Multiple Myeloma|
|Anticipated Study Start Date :||January 2018|
|Estimated Primary Completion Date :||January 2023|
|Estimated Study Completion Date :||January 2023|
This is a single arm phase II trial to assess the Very Good Partial Response rate of a strategy involving autologous hematopoietic stem cell transplantation, after intensive treatment and followed by consolidation phase, with elotuzumab, dexamethasone, velcade, and thalidomide in elderly patients.
Induction treatment 4 cycles of 28 days: Elotuzumab IV, 10 mg/Kg, D1, 8, 15, 22 Dexamethasone PO, 40 mg/d, D1, 8, 15 Velcade® IV, 1,3 mg/m2/d, D1, 4, 8, 11 Thalidomide PO, 100 mg/d, D1 to 21
2 cycles of 28 days (2 to 3 months after autograft) Elotuzumab IV, 10 mg/Kg, D1, 8, 15 and 22 Dexamethasone PO, 40 mg/d, D1, 8 and 15 Velcade® IV, 1,3 mg/m2/d, D1, 4, 8, and 11 Thalidomide® PO, 100 mg/d, D1 to 21
Other Name: Empliciti®
- Maximal response rate Assesment of the International Myeloma Working Group uniform response criteria [ Time Frame: 1 month after the last consolidation cure ]Assesment of the International Myeloma Working Group uniform response criteria
- survival and progression-free survival [ Time Frame: one year after the last consolidation cure ]Survival rate and global follow-up
- evaluation of the answer to the treatment to improve or maintain the response [ Time Frame: 12 month of treatment from inclusion ]Best response obtained or maintained for each therapeutical phase
- Role of the consolidation phase in the improvement or maintenance of the response to the treatment Time before progression [ Time Frame: From inclusion to month 36 ]Time before progression
- Conversion from negative residual disease to positive residual disease or maintenance of a negative residual disease during all therapeutical phases [ Time Frame: from inclusion to month 36 ]Conversion rate from negative residual disease to positive residual disease or maintenance of a negative residual disease during induction, IT with AHSC (autograft of hematopoietic stem cells) and consolidation
- correlation between residual disease and duration of the response to the treatment [ Time Frame: From inclusion to the end of the 12 treatment-month ]Comparison of response duration, overall survival and event-free survival between patients with negative residual disease and the other patients, after the induction phase and at the end of the treatment phase
- Tolerance to each phase of treatment (the induction phase, the intensive treatment, the consolidation phase) [ Time Frame: From inclusion to month 36 ]Tolerance to each therapeutical phase will be assessed with ECOG (Eastern Cooperative Oncology Group) performance status, adverse events rate, serious adverse events rate and biological parameters
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03393273
|Contact: Mohamad Mohty, PU-PHemail@example.com|
|Contact: Florent Malard, CCU-AHfirstname.lastname@example.org|
|Principal Investigator:||Mohamad Mohty, PU-PH||Assistance Publique - Hôpitaux de Paris|