NCT01084252

Phase 1/2 Dose Escalation and Efficacy Study of Anti-CD38 Monoclonal Antibody in Patients With Selected CD38+ Hematological Malignancies

A Phase I/2 Dose Escalation Safety, Pharmacokinetic and Efficacy Study of Multiple Intravenous Administrations of a Humanized Monoclonal Antibody (SAR650984) Against CD38 in Patients With Selected CD38+ Hematological Malignancies

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 351 (actual)
• Sponsor: Sanofi · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Primary Objective: Phase 1: To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984 (Isatuximab). Phase 2 (stage 1): To evaluate the activity of single-agent Isatuximab at different doses/schedules and to select dose and regimen to further evaluate the overall response rate (ORR) of Isatuximab as single agent or in combination with dexamethasone. Phase 2 (stage 2): To evaluate the activity in terms of overall response rate (ORR) of Isatuximab at the selected dose/schedule from stage1, as single agent (ISA arm) and in combination with dexamethasone (ISAdex arm). Secondary Objectives: Phase 1: * To characterize the global safety profile including cumulative toxicities. * To evaluate the pharmacokinetic (PK) profile of Isatuximab in the proposed dosing schedule(s). * To assess the pharmacodynamics (PD), immune response, and preliminary disease response. Phase 2 (stage 1): to evaluate the following objectives for Isatuximab as single agent: * Safety * Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival. Phase 2 (stage 2): to evaluate the following objectives in each arm (ISA and ISAdex): * Safety * Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival. * Participant-reported changes in health-related quality of life, symptoms of multiple myeloma and generic health status. * Pharmacokinetic profile of Isatuximab. * Immunogenicity of Isatuximab. * Investigate the relationship between CD38 receptor density and CD38 receptor occupancy (Stage 1 only) on multiple myeloma cells and parameters of clinical response.

Detailed description

The Phase 1 study duration for an individual participant included a screening period for inclusion of up to 2 weeks, treatment with Isatuximab QW (every week) or Q2W (every 2 weeks) unless discontinued earlier due to safety or disease progression. Participants were followed for a minimum of 30 days following the last use of study drug or more than 30 days in case of unresolved toxicity, or up to initiation of another anticancer treatment. The Phase 2 study duration for an individual participant included a screening period for inclusion of up to 3 weeks, then a treatment period and a follow up period. Treatment was continued until disease progression, unacceptable adverse reactions or other reasons for discontinuation. Participants were followed every 3 months following the last use of study drug until death or study cutoff, whichever came first.

Conditions

• Hematological Malignancy

Interventions

Type	Name	Description
DRUG	Isatuximab SAR650984	Pharmaceutical form: solution for infusion Route of administration: intravenous
DRUG	Dexamethasone	Pharmaceutical form: solution for infusion Route of administration: intravenous
DRUG	Dexamethasone	Pharmaceutical form: tablet Route of administration: oral

Timeline

• Start date: 2010-05-11
• Primary completion: 2018-12-21
• Completion: 2023-07-13
• First posted: 2010-03-10
• Last updated: 2024-11-01
• Results posted: 2020-04-15

Locations

59 sites across 17 countries: United States, Argentina, Belgium, Brazil, Chile, Finland, France, Greece, Israel, Italy, Mexico, Peru, Russia, Spain, Turkey (Türkiye), Ukraine, United Kingdom

Regulatory

• FDA-regulated drug study