Study of Isatuximab Combined With Bortezomib + Cyclophosphamide + Dexamethasone (VCD) and Bortezomib + Lenalidomide + Dexamethasone (VRD) in Newly Diagnosed Multiple Myeloma (MM) Non Eligible for Transplant or No Intent for Immediate Transplantation
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|ClinicalTrials.gov Identifier: NCT02513186|
Recruitment Status : Recruiting
First Posted : July 31, 2015
Last Update Posted : August 13, 2019
- To determine the maximum tolerated dose (MTD) and recommended dose (RD) of isatuximab when administered in combination with bortezomib, cyclophosphamide, and dexamethasone (VCDI) based on the dose-limiting toxicity(ies) (DLTs) observed in patients with newly diagnosed multiple myeloma non-eligible for transplantation.
- To evaluate safety and preliminary efficacy (overall response rate and complete response rate) of isatuximab in combination with bortezomib, dexamethasone, and cyclophosphamide in patients with newly diagnosed multiple myeloma non-eligible for transplantation.
VRDI cohort parts A and B:
- To evaluate preliminary efficacy (complete response rate) of isatuximab in combination with bortezomib, dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma non-eligible for transplantation or no intent for immediate transplantation.
- To characterize the overall safety profile of isatuximab in combination with each bortezomib-based regimen, including cumulative toxicities.
- To characterize the pharmacokinetic (PK) profile of isatuximab and each combination drug in each isatuximab/bortezomib based regimen.
- To evaluate the immunogenicity of isatuximab in combination treatments.
- To evaluate the preliminary efficacy of both bortezomib based regimens in terms of duration of response, overall response rate and progression-free survival.
- To assess the relationship between clinical effects (adverse event [AE] and/or tumor response) and CD38 receptor density (VCDI and VRDI part only).
- To evaluate the infusion duration.
- To assess the minimal residual disease (MRD) negativity rate in patients achieving a Complete Response (CR) or Very Good Partial Response (VGPR).
|Condition or disease||Intervention/treatment||Phase|
|Plasma Cell Myeloma||Drug: lenalidomide Drug: bortezomib Drug: cyclophosphamide Drug: dexamethasone Drug: isatuximab SAR650984||Phase 1|
The duration of the study for an individual patient will include:
- A period to assess eligibility (screening or baseline period) of up to 3 weeks for VCDI cohort, up to 28 days for VRDI cohort;
- for patients in the VCDI cohort: a treatment period including up to 12 induction treatment cycles (50-week duration).
- for patients in the VRDI cohort: a treatment period including up to 4 induction cycles (24 week duration).
- Following induction, both cohorts have maintenance periods consisting of 4 week cycles until progression, unacceptable AE, or patient willingness to discontinue and an end-of-treatment visit at least 30 days following the last administration of treatment.
- Patients that discontinue therapy for reasons other than progression will have follow-up visits until progression or until the patient receives another anticancer therapy, whichever is earlier.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||88 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Dose Escalation, Safety, Pharmacokinetic, Pharmacodynamic and Preliminary Efficacy Study of SAR650984 (Isatuximab) Administered Intravenously in Combination With Bortezomib - Based Regimens in Adult Patients With Newly Diagnosed Multiple Myeloma Non Eligible for Transplantation or No Intent for Immediate Transplantation|
|Actual Study Start Date :||September 30, 2015|
|Estimated Primary Completion Date :||October 2022|
|Estimated Study Completion Date :||October 2022|
VCDI cohort: Isatuximab (escalating dose) + bortezomib + cyclophosphamide + dexamethasone (VCDI): Induction phase will be 50 weeks (12 cycles). The duration of a cycle will be 42 days (6 weeks) for Cycle 1 (C1) and 28 days (4 weeks) for subsequent cycles. The duration of a cycle of the maintenance phase will be 28 days (4 weeks). After C12, isatuximab will be administered at its initial assigned dose and dexamethasone once every 28 days.
VRDI cohort parts A and B: Isatuximab + bortezomib + dexamethasone + lenalidomide (VRDI): Induction phase will be 24 weeks (4 cycles at 6 weeks/cycle). The duration of a cycle of the maintenance phase will be 28 days (4 weeks). Maintenance therapy may continue until disease progression, unacceptable AE or patient willingness to discontinue.
VRDI Part A: Enrollment to begin after the VCDI cohort is completed.
VRDI Part B: Enrollment to begin after the VRDI part A is completed.
Pharmaceutical form: tablet Route of administration: oral
Other Name: Revlimid
Pharmaceutical form: lyophilized powder for subcutaneous injection Route of administration: subcutaneous
Other Name: Velcade
Pharmaceutical form: tablet Route of administration: oral
Other Name: Endoxan
Pharmaceutical form: tablet or solution for infusion Route of administration: oral or intravenous
Drug: isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous
- Assessment of dose-limiting toxicities (DLTs) in VCDI cohort [ Time Frame: Up to 6 weeks per treated patient ]
- Overall response rate (VCDI) [ Time Frame: Up to 34 weeks of treatment (induction phase) ]
- Complete response rate (VCDI) [ Time Frame: Up to 34 weeks of treatment (induction phase) ]
- Complete response rate (VRDI) [ Time Frame: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]
- Number of patients with adverse events (AEs), clinically significant changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling [ Time Frame: VCDI: Up to approximately 106 weeks, VRDI Part A and Part B: Up to approximately 104 weeks ]
- Overall response rate (VRDI) [ Time Frame: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]
- Infusion duration [ Time Frame: VRDI Part B: Up to 104 weeks of treatment ]
- Assessment of PK parameter: Partial area under the serum concentration time curve (AUC) [ Time Frame: VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks ]
- Assessment of PK parameter: Maximum observed concentration (Cmax) [ Time Frame: VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks ]
- Levels of human antidrug antibodies (ADA) [ Time Frame: VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks ]
- Duration of response - time [ Time Frame: VCDI and VRDI: Until treatment discontinuation by the last patient ]
- Progression-free survival for VCDI [ Time Frame: VCDI: 30 months after LPI ]
- Progression-free survival for VRDI [ Time Frame: VRDI Part A and Part B: 24 months after LPI ]
- MRD negativity rate [ Time Frame: Up to 3 years of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02513186
|Contact: Trial Transparency email recommended (Toll free number for US & Canada)||800-633-1610 ext 1 then #||Contact-Us@sanofi.com|
|Investigational Site Number 250002||Recruiting|
|Nantes Cedex 01, France, 44093|
|Investigational Site Number 250003||Recruiting|
|Pierre Benite, France, 69495|
|Investigational Site Number 250001||Recruiting|
|Toulouse Cedex 9, France, 31059|
|Investigational Site Number 276003||Recruiting|
|Berlin, Germany, 12200|
|Investigational Site Number 276002||Recruiting|
|Leipzig, Germany, 04103|
|Investigational Site Number 380003||Recruiting|
|Milano, Italy, 20132|
|Investigational Site Number 380002||Recruiting|
|Roma, Italy, 00161|
|Investigational Site Number 380001||Recruiting|
|Torino, Italy, 10126|
|Investigational Site Number 724003||Recruiting|
|Madrid, Spain, 28041|
|Investigational Site Number 724001||Recruiting|
|Pamplona, Spain, 31008|
|Investigational Site Number 724002||Recruiting|
|Salamanca, Spain, 37007|
|Investigational Site Number 724004||Recruiting|
|Santander, Spain, 39008|
|Study Director:||Clinical Sciences & Operations||Sanofi|