Isatuximab in Combination With Novel Agents in RRMM - Master Protocol

Brief description of study

The purpose of this umbrella study is to evaluate isatuximab when combined with novel agents with or without dexamethasone in participants with relapsed or refractory myeloma.

Detailed description of study

Approximately 28 months

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

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, 02 (Terminated), 03 (Terminated): 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: Participants must be exposed to anti-CD38 and anti-BCMA therapy

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.
  • Hemoglobin <8 g/dL.
  • Platelets <50 x 10^9/L.
  • Absolute neutrophil count <1.5 x 10^9/L.
  • Creatinine clearance <30 mL/min.
  • Total bilirubin >1.5 x ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 x ULN.
  • Aspartate aminotransferase and/or alanine aminotransferase >3 x 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 02 (terminated):
    • 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 (terminated):
    • 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.
        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.

Updated on 21 Mar 2023 . Study ID: NCT04643002

Find a site

What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact