Isatuximab in Combination With Novel Agents in RRMM - Master Protocol
Brief description of study
- Part 1 (dose finding, experimental substudies):
-To determine or confirm the recommended dose of novel agents when combined with 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
- -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.
Detailed description of study
Approximately 28 months
Clinical Study Identifier: NCT04643002
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Plasma Cell Myeloma Refractory
Age: 18 Years
Gender: Male or Female
- 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 01-03:
- 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.
- Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma.
- Uncontrolled infection within 14 days prior to randomization.
- Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to randomization, 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 randomization: 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 randomization.
- Any anti-MM drug treatment within 14 days before randomization, including dexamethasone.
- Participants with a contraindication to treatment.
- Vaccination with a live vaccine 4 weeks before the start of the study.
- Hemoglobin <8 g/dL.
- Platelets <50 × 109/L.
- Absolute neutrophil count <1.5 × 109/L.
- Creatinine clearance <30 mL/min.
- 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.
- For the first 10 participants: Body weight ≤70 kg
- Substudy 03:
- Current corneal epithelial disease except mild punctate keratopathy
- Patients who have received prior therapy with belantamab mafodotin
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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