Phase Ib Study of SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT02332850|
Recruitment Status : Recruiting
First Posted : January 7, 2015
Last Update Posted : October 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Biological: Isatuximab Drug: Carfilzomib Drug: Dexamethasone||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||118 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multi-ARM Phase Ib Study of SAR650984 (Isatuximab, an Anti-CD38 mAb) in Combination With Standard Carfilzomib, and High-dose Weekly Carfilzomib and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma|
|Actual Study Start Date :||January 21, 2015|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2024|
Experimental: Arm I (20 mg dexamethasone, isatuximab, carfilzomib)
20 mg dexamethasone IV given on days 1, 8, 15, 22 (pre- SAR650984 and carfilzomib), then dexamethasone 4 IV or PO mg Day 2, 9, 16.
All patients will receive a fixed dose of Isatuximab (SAR650984) according to their assigned dose cohort. Patients receive isatuximab IV over 4-6 hours on days 1 and 15 of every cycle for the starting cohort, and days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Carfilzomib IV will be administered over 10 minutes on days 1, 2, 8, 9, 15, and 16 . Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue treatment after 8 courses if clinical benefit is present at the investigator's discretion (carfilzomib may be switched to days 1, 2, 15, and 16 after 8 cycles per investigator discretion).
Other Name: SAR 650984
Given IV or PO
Experimental: Arm II (40 mg dexamethasone, isatuximab, carfilzomib)
40 mg dexamethasone IV given on Days 1, 8, 15 and 22 (use as premed to isatuximab).
All patients will receive a fixed dose of Isatuximab (SAR650984) according to the assigned dose. Patients receive isatuximab IV over 4-6 hours on day 1, 3-4 hours on Day 8, 15, and 22 of cycle 1 and then on days 1 and 15 of subsequent cycle (patients may be eligible for rapid siatuximab given over 75 minutes), and carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: SAR 650984
Given IV or PO
- ARM I: Incidence of Dose-Limiting Toxicities (DLT) [ Time Frame: Up to 60 days of the last dose of study drug ]Treatment-related Adverse events resulting in a DLT will be summarized by maximum toxicity grade for each dose level of isatuximab.
- ARM I: Maximum tolerated dose (MTD) of isatuximab [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]The MTD is defined as the dose level below the lowest dose that induces dose- limiting toxicity in at least one-third of patients Adverse events will be summarized by maximum toxicity grade and by dose level for each ARM of the trial using NCI CTCAE v4.03
- ARM II: Overall Response Rate (ORR) [ Time Frame: Up to 60 days of the last dose of study drug ]Overall response rate (ORR) as define by the International Myeloma Working Group (IMWG) uniform response criteria of patients obtaining Stringent Complete Remission (sCR), Complete Remission (CR), Very Good Partial Remission (VGPR), Partial Remission (PR), or Minimal Remission (MR)
- ARM I: Pharmacokinetic (PK) profile of isatuximab [ Time Frame: Baseline, 2 hours mid-infusion, 4, 7, and 11 hours after end of infusion on day 1, days 2, 3, 8, and 15 of course 1, and 0 and 4 hours after end of infusion on day 1 of courses 2-8 (and 0 hours on day 15 of course 2 only) ]Individual plasma concentrations and PK parameters of SAR650984 will be tabulated with standard descriptive statistics. Pharmacokinetic analyses will be carried out in the Pharmacokinetics, Dynamics and Metabolism Department at Sanofi for SAR650984 and carfilzomib.
- ARM I: Overall Response Rate (ORR) [ Time Frame: Up to 60 days of the last dose of study drug ]Overall response rate; defined as sCR+CR+VGPR + PR utilizing IMWG Uniform Response Criteria
- ARM I: Clinical benefit response (CBR) [ Time Frame: Up to 60 days of the last dose of study drug ]defined as CR + VGPR + PR + minor response (MR), utilizing International Myeloma Working Group (IMWG) Uniform Response Criteria
- ARM I: Incidence of isatuximab-specific antidrug antibodies (ADA) [ Time Frame: Up to 1 year ]Analysis to be performed by Sanofi-Oncology
- ARM I: Percentage of bone marrow cells expressing cell surface determinant, CD38 and receptor density [ Time Frame: Up to 30 days of the last dose of study drug ]
- Overall survival (OS) [ Time Frame: assessed at 1, 2, and 3 years from start of treatment ]Duration of time from start of treatment to death on study from any cause,
- Progression Free Survival (PFS) [ Time Frame: from start of treatment up to 1 year ]Duration of time from start of treatment to the first occurrence of disease progression or death on study from any cause, whichever occurs earlier,
- Time To Progression (TTP) [ Time Frame: from start of treatment up to 1 year ]Defined as the duration from start of treatment until the first occurrence of disease progression with deaths from causes other than disease progression, censored
- Duration of Response (DOR) [ Time Frame: up to 60 days of the last dose of study drug ]The duration of overall response is defined as the time period when criteria are met for MR or better (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. The duration of CR is defined as the time when criteria are first met for CR until the first date that IMWG relapse is objectively documented
- Changes in pharmacodynamics variables as they relate to dose, response, and toxicity of carfilzomib in combination with isatuximab [ Time Frame: Baseline to up to 30 days of the last dose of study drug ]Changes from baseline in pharmacodynamic markers and proliferation markers, will be evaluated and summarized for each dose cohort.
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): NCT02332850
|Contact: Phu Lamemail@example.com|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Phu Lam 877-827-3222 firstname.lastname@example.org|
|Principal Investigator: Thomas Martin, MD|
|United States, New Jersey|
|Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: David Vesole, MD 551-996-5900 David.Vesole@hackensackmeridian.org|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Ajai Chari, MD 212-241-7873 Ajai.Chari@mountsinai.org|
|Principal Investigator:||Thomas Martin, MD||University of California, San Francisco|