Multiple Myeloma Clinical Trial

Isatuximab in Combination With Novel Agents in RRMM – Master Protocol

Summary

Primary Objectives:

Part 1 (dose finding, experimental substudies):

-To determine or confirm the recommended dose of novel agents when combined with treatment-a-promising-new-option-for-relapsed-multiple-myeloma/" >isatuximab with or without dexamethasone in participants with RRMM.

Part 2 (expansion, experimental substudies):

To demonstrate the clinical benefit of novel agents combined with isatuximab with or without dexamethasone in terms of rate of very good partial response (VGPR) or better

Secondary Objectives:

-Master Protocol and Substudy 1-ACT16482-01 (Control Arm):
To assess the overall response rate (ORR) in each treatment arm.
To assess the clinical benefit rate (CBR) in each treatment arm.
To assess the duration of response (DOR) in each treatment arm.
To assess the time to first response (TT1R) in each treatment arm.
To assess the time to best response (TTBR) in each treatment arm.
To assess safety and tolerability in each treatment arm.
To assess progression free survival (PFS) in each treatment arm.
To assess overall survival (OS) in each treatment arm.
To evaluate the potential immunogenicity of isatuximab and novel agents when applicable.
To characterize the PK of isatuximab and novel agents.
To assess disease and treatment related symptoms, cancer and disease specific health-related quality of life, global impact of side effects and confirm/establish clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores.
-Substudy 3-ACT16482-03:
To assess patient-reported visual functioning.

View Full Description

Full Description

Participants will continue study treatment until disease progression, death, unacceptable toxicity, participant request to stop treatment, Investigator decision, or study termination by the Sponsor i.e., up to Aapproximately 28 months.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Participant must be 18 years of age inclusive or older.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Participants with relapsed or refractory MM who have received at least 3 prior lines of therapy for MM, including PIs and IMiDs or at least 2 prior lines if at least one of these lines consisted of 2 or more multiagent regimens (eg, Induction regimen with autologous stem cell transplant followed by maintenance).

RRMM with measurable disease:

Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
Serum free light chain (sFLC) MM without measurable M protein in serum or urine per previous criteria (serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio <0.26 or >1.65).
Men or woman or childbearing potential should agree to use contraception.
Substudy 01, 06: Anti-CD38 therapy naïve or prior exposure to such drugs with a wash out of at least 6 months after the last dose. "Exposure" is defined as at least 2 cycles of therapy.
Substudies 02, 03: Anti-CD38 therapy naïve or prior exposure to such drugs without being refractory but with a wash out of at least 6 months after the last dose. "Refractory" is defined as progressing within 60 days of last dose of anti-CD38 targeting therapy.
Substudy 04: Anti-CD38 and anti-B cell maturation antigen (BCMA) therapy prior exposed participants with RRMM.
Substudy 05: Participants with RRMM with at least 2 cycles of prior exposure to anti-CD38 therapy. For participants to whom BCMA targeted therapy is available (ie, approved in their region and can be reimbursed), at least 2 cycles of prior exposure to a BCMA targeted agent is mandatory.

Exclusion Criteria:

Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma.
Uncontrolled infection within 14 days prior to first study intervention administration.
Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to first study intervention administration., eg, myocardial infarction, unstable angina, coronary (eg, coronary artery bypass graft, percutaneous coronary intervention) or peripheral artery revascularization, left ventricular ejection fraction <40%, heart failure New York Heart Association Classes III and IV, stroke, transient ischemic attack, pulmonary embolism, other thromboembolic event, or cardiac arrhythmia (Grade 3 or higher by NCI CTCAE Version 5.0).
Known acquired immunodeficiency syndrome-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A.
Uncontrolled or active hepatitis B virus (HBV) infection.
Active hepatitis C virus (HCV) infection.
Any of the following within 3 months prior to first study intervention administration: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease.
Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma, unless they are successfully treated with curative intent for more than 3 years before first study intervention administration.
Any anti-MM drug treatment within 14 days before first study intervention administration, including dexamethasone.
Participants with a contraindication to treatment.
Vaccination with a live vaccine 4 weeks before the start of the study.
Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
Hemoglobin <8 g/dL.
Platelets <50 × 10^9/L.
Absolute neutrophil count <1.5 × 10^9/L.
Creatinine clearance <30 mL/min/1.73m2.
Total bilirubin >1.5 × ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 × ULN.
Aspartate aminotransferase and/or alanine aminotransferase >3 × ULN.
Patients with grade 3 or 4 hypercalcemia.

Substudy 01:

-Malabsorption syndrome or any condition that can significantly impact the absorption of pomalidomide.

Substudy 02:

History of resected/ablated basal or squamous cell carcinoma (SCC) of the skin or carcinoma in situ of the cervix, or other local tumors, even if considered cured by local treatment.
Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior to the first dose of SAR439459.
Prothrombin time or INR >1.5 × upper limit of normal (ULN).

Substudy 03:

Current corneal epithelial disease except mild punctate keratopathy
Patients who have received prior therapy with belantamab mafodotin

Substudy 04:

Central nervous system or leptomeningeal disease.
Medical history of seizure.
Participants currently receiving hepatically metabolized narrow therapeutic index drugs (eg, digoxin, warfarin) if cannot be closely monitored.

Substudy 05:

- Participant unable to swallow tablets

Substudy 06:

History of active autoimmune disorders
History of autoimmune hemolytic anemia or autoimmune thrombocytopenia
Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD
Prior allogenic hematopoietic stem cell transplant (allo-HSCT)
Hemoglobin < 9g/dL
Prior therapy with any anti-CD47 or anti signal regulatory protein alpha agent

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study is for people with:

Multiple Myeloma

Phase:

Phase 1

Estimated Enrollment:

197

Study ID:

NCT04643002

Recruitment Status:

Recruiting

Sponsor:

Sanofi

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There are 19 Locations for this study

See Locations Near You

University of Illinois Site Number : 8400007
Chicago Illinois, 60612, United States
University of Michigan Site Number : 8400004
Ann Arbor Michigan, 48109, United States
Roswell Park Cancer Institute Site Number : 8400008
Buffalo New York, 14263, United States
Investigational Site Number : 0360006
Wollongong New South Wales, 2500, Australia
Investigational Site Number : 0360002
Fitzroy Victoria, 3065, Australia
Investigational Site Number : 0360001
Richmond Victoria, 3121, Australia
Investigational Site Number : 2500002
Lille , 59037, France
Investigational Site Number : 2500001
Nantes , 44093, France
Investigational Site Number : 2500003
Paris , 75013, France
Investigational Site Number : 2500004
Paris , 75015, France
Investigational Site Number : 2760006
Frankfurt am Main , 60590, Germany
Investigational Site Number : 3000002
Athens , 10676, Greece
Investigational Site Number : 3000001
Athens , 11528, Greece
Investigational Site Number : 3800001
Meldola Forlì-Cesena, 47014, Italy
Investigational Site Number : 3800002
Bologna , 40138, Italy
Investigational Site Number : 5780001
Oslo , 0450, Norway
Investigational Site Number : 6200001
Coimbra , 3000-, Portugal
Investigational Site Number : 6200002
Vila Nova Gaia , 4434-, Portugal
Puerto Rico Medical Research Center, LLC Site Number : 8400005
Hato Rey , 00917, Puerto Rico

How clear is this clinincal trial information?

Study is for people with:

Multiple Myeloma

Phase:

Phase 1

Estimated Enrollment:

197

Study ID:

NCT04643002

Recruitment Status:

Recruiting

Sponsor:


Sanofi

How clear is this clinincal trial information?

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