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

Completed · Phase 1/Phase 2

Conditions studied: Hematological Malignancy

In brief

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.

Key facts

Study ID

NCT01084252

Run by

Sanofi

People needed

351

Starts

2010-05-11

Expected to finish

2023-07-13

Last updated by the study team

2024-11-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Phase 1:
• For dose escalation cohorts, participants with confirmed selected CD38+ hematological malignancies as specified below who had progressed on after standard therapy or for whom there was no effective standard therapy (refractory/relapsed participants). B-cell Non-Hodgkin-lymphoma/leukemia (NHL) participants with at least 1 measurable lesion. Multiple myeloma (MM) participants with measurable M-protein serum and/or 24-hour urine. Acute myeloid leukemia (AML) participants, all types except M3 based on French-American-British (FAB) classification. Acute Lymphoblastic Leukemia (B-cell ALL) participants. Chronic lymphocytic leukemia (CLL) participants.
• For expansion cohorts, participants with relapsed/refractory MM with measurable M-protein (serum M-protein of >0.5 g/dL and/or urine M-protein of >200 mg (24-hr urine)) or elevated serum free light chains (FLC) >10 mg/dL with abnormal FLC ratio) who had progressed on or after standard therapy that included an Immunomodulatory drug (IMiD) and a proteasome inhibitor and who met the protocol defined criteria for standard risk or high risk.
• Phase 2:
• Participants had a known diagnosis of multiple myeloma with evidence of measurable disease, and have evidence of disease progression based on International Myeloma Working Group (IMWG) criteria: Serum M-protein ≥1 g/dL, or urine M-protein >=200 mg/24 hours or in the absence of measurable m-protein, serum FLC >=10 mg/dL, and abnormal serum immunoglobulin kappa lambda FLC ratio (<0.26 or >1.65).
• Participants who received at least three prior lines of therapy for MM and had treatment with an IMiD (for >=2 cycles or >=2 months of treatment) and a proteasome inhibitor (PI) (for >=2 cycles or >=2 months of treatment) OR participants whose disease was double refractory to an IMiD and a PI. For participants who had received more than 1 type of IMiD and PI, their disease must be refractory to the most recent one.
• Participants who had achieved a minimal response or better to at least one prior line of therapy.
• Participants who had received an alkylating agent (>=2 cycles or >=2 months) either alone or in combination with other MM treatments.
• Stage 2 only: Participants who had evidence of disease progression on or after the most recent prior regimen based on IMWG criteria.

You may not qualify if…

• Phase 1:
• Karnofsky performance status <60
• Poor bone marrow reserve
• Poor organ function
• Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that was not amenable to pre-medication with steroids and H2 blockers
• Any serious active disease (including clinically significant infection that was chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, interfered with the safety, the compliance with the study or with the interpretation of the results
• Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results
• Phase 2:
• Participants with multiple myeloma immunoglobulin M (IgM) subtype
• Previous treatment with any anti-CD38 therapy
• Participants with concurrent plasma cell leukemia
• Participants with known or suspected amyloidosis
• Karnofsky performance status <60 (stage 1)/Eastern Cooperative Oncology Group (ECOG) Performance status >2 (stage 2).
• Poor bone marrow reserve
• Poor organ function
• Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that was not amenable to pre-medication with steroids and H2 blockers
• Any serious active disease (including clinically significant infection that was chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, interfered with the safety, the compliance with the study or with the interpretation of the results
• Any severe underlying medical conditions including presence of laboratory abnormalities, which impaired the ability to participate in the study or the interpretation of its results
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Where it is running

• UCSF MS Center Site Number : 840005 — San Francisco, California, United States
• Emory University Site Number : 840009 — Atlanta, Georgia, United States
• University of Chicago Site Number : 840010 — Chicago, Illinois, United States
• The University Of Michigan Site Number : 840022 — Ann Arbor, Michigan, United States
• Karmanos Cancer Center Site Number : 840027 — Detroit, Michigan, United States
• Mayo Clinic of Rochester Site Number : 840018 — Rochester, Minnesota, United States
• Washington University School of Medicine Site Number : 840013 — St Louis, Missouri, United States
• The Cancer Center At Hackensack University Medical Site Number : 840011 — Hackensack, New Jersey, United States
• Memorial Sloan-Kettering Cancer Center Site Number : 840014 — New York, New York, United States
• Duke University Medical College Site Number : 840016 — Durham, North Carolina, United States
• University of Cincinnati Site Number : 840004 — Cincinnati, Ohio, United States
• Vanderbilt University Site Number : 840001 — Nashville, Tennessee, United States
• Huntsman Cancer Institute at the University of Utah Site Number : 840002 — Salt Lake City, Utah, United States
• Fred Hutchinson Cancer Research Center Site Number : 840012 — Seattle, Washington, United States
• Medical College of Wisconsin Site Number : 840017 — Milwaukee, Wisconsin, United States
• Investigational Site Number : 032003 — Capital Federal, Buenos Aires, Argentina
• Investigational Site Number : 032002 — Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
• Investigational Site Number : 032001 — Ciudad de Buenos Aires, Buenos Aires, Argentina
• Investigational Site Number : 056001 — Antwerp, Belgium
• Hospital Mae de Deus Site Number : 076003 — Porto Alegre, Rio Grande do Sul, Brazil
• Hospital de Amor - Hospital do Cancer de Barretos - Fundacao Pio XII Site Number : 076001 — Barretos, São Paulo, Brazil
• Clínica São Germano Site Number : 076002 — São Paulo, São Paulo, Brazil
• Instituto COI de Educacao e Pesquisa Site Number : 076004 — Rio de Janeiro, Brazil
• Investigational Site Number : 152001 — Temuco, La Araucanía, Chile
• Mayo Clinic Site Number : 840003 — Scottsdale, Arizona, United States

Full record on ClinicalTrials.gov

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