NCT02332850

Phase Ib Study of SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma

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

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 83 (actual)
• Sponsor: Thomas Martin, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the side effects and best dose of isatuximab when given together with carfilzomib with or without dexamethasone and lenalidomide in treating patients with multiple myeloma that has returned after a period of improvement (relapsed) or has not respond to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as isatuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving isatuximab and carfilzomib with or without dexamethasone and lenalidomide may be a better treatment for patients with multiple myeloma.

Detailed description

PRIMARY OBJECTIVES: ARM 1: To determine the maximum tolerated dose (MTD) of SAR650984 in combination with standard carfilzomib (Arm 1 is complete). ARM 2: To determine the safety AND efficacy (objective response rate (ORR)) of adding SAR650984 10mg/kg weekly x 4 doses then every other week in combination with weekly carfilzomib (70 mg/m2) and dexamethasone, in patients with relapsed or refractory myeloma. ORR will be defined using the International Myeloma Working Group (IMWG) uniform response criteria. SECONDARY OBJECTIVES: ARM 1: 1. To evaluate the safety, including immunogenicity (ARM 1), of SAR650984 in combination with carfilzomib, in patients with relapsed or refractory myeloma after receiving 1+ prior lines of therapy. The severity, frequency and incidence of all toxicities will be assessed. 2. To evaluate the pharmacokinetics (PK) of SAR650984 and carfilzomib when administered in ARM 1 (completed). 3. To assess the relationship between clinical (adverse event and/or tumor response) effects and pharmacologic parameters (PK/PD), and/or biologic (correlative laboratory) results. 4. To estimate the activity (ORR) using the International Myeloma Working Group (IMWG) defined response criteria of SAR650984 plus carfilzomib (ARM 1) 5. To describe progression free survival (PFS), time to disease progression (TTP) and 1-year overall survival (OS) in patients treated with SAR650984 plus standard carfilzomib, and SAR650984 with weekly carfilzomib and dexamethasone. EXPANSION COHORTS: ARM 1: 1\. To further evaluate safety, PK, PD and to estimate the anti-tumor activity (response rates) using IMWG defined response criteria of study therapy (SAR650984 plus carfilzomib). ARM 1 and 2: 1\. To describe progression-free survival, 1-year OS, and TTP in patients with relapsed or refractory myeloma treated with these combinations. OUTLINE: This is a dose-escalation study of isatuximab. Patients are randomized to 1 of 2 arms. ARM I: Patients receive dexamethasone intravenously (IV) on days 1, 8, 15, and 22 of cycle 1, and orally (PO) or IV on days 1 and 15 of subsequent cycles. Patients receive isatuximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles, and carfilzomib IV over 10 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment after 8 cycles if clinical benefit is present at the investigator's discretion (carfilzomib may be switched to days 1, 2, 15, and 16 per investigator discretion). ARM II: Patients receive dexamethasone IV or PO on days 1, 8, 15, and 22, isatuximab IV over 4-6 hours on 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles, and carfilzomib IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 and 60 days and then every 3 months for up to 3 years.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
BIOLOGICAL	Isatuximab	Given IV
DRUG	Carfilzomib	Given IV
DRUG	Dexamethasone	Given IV or PO

Timeline

• Start date: 2015-01-21
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2015-01-07
• Last updated: 2025-05-01

Locations

6 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study