Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients
Condition: Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Isatuximab; Pomalidomide; Dexamethasone
Intervention description: Pharmaceutical form: solution for infusion Route of administration: intravenous; Pharmaceutical form: capsule Route of administration: oral; Pharmaceutical form: tablets or solution for infusion Route of administration: oral or intravenous
Intervention MeSH terms: Dexamethasone; Pomalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 307.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Anti-CD38 monoclonal antibody

Summary:

      Primary Objective:

      To demonstrate the benefit of isatuximab in combination with pomalidomide and low-dose
      dexamethasone in the prolongation of Progression Free Survival (PFS) as compared to
      pomalidomide and low-dose dexamethasone in participants with refractory or relapsed and
      refractory multiple myeloma (MM).

      Secondary Objectives:

        -  To evaluate the Overall Response Rate (ORR) as per International Myeloma Working Group
           (IMWG) criteria in each arm.

        -  To compare the Overall Survival (OS) between the two arms.

        -  To evaluate the Time To Progression (TTP) in each arm.

        -  To evaluate the PFS in high risk cytogenetic population in each arm.

        -  To evaluate the Duration of Response (DOR) in each arm.

        -  To evaluate the safety in both treatment arms.

        -  To determine the Pharmacokinetic profile of isatuximab in combination with pomalidomide.

        -  To evaluate the immunogenicity of isatuximab.

        -  To assess disease-specific and generic health-related quality of life (HRQL), disease
           and treatment-related symptoms, health state utility, and health status.
    

Eligibility criteria:

        Inclusion criteria :

          -  Age superior or equal to 18 years or country's legal age of majority if the legal age
             was superior to 18 years old.

          -  Participants had a documented diagnosis of multiple myeloma with evidence of
             measurable disease i.e. serum M protein superior or equal to 0.5 grams per decilitre
             (g/dL) measured using serum protein immunoelectrophoresis and or urine M protein
             superior or equal to 200 mg per 24 hours measured using urine protein
             immunoelectrophoresis.

          -  Participants had received at least 2 prior lines of anti-myeloma therapy, which must
             include at least 2 consecutive cycles of lenalidomide and a proteasome inhibitor
             (bortezomib, carfilzomib or ixazomib) given alone or in combination.

          -  Participants had failed treatment with lenalidomide and a proteasome inhibitor
             (bortezomib, carfilzomib, or ixazomib) alone or in combination (Intolerant,
             progression within 6 months after reaching Partial Response or better).

          -  Participants had progressed on or within 60 days after end of previous therapy before
             to study entry, i.e., refractory to the last line of treatment.

        Exclusion criteria:

          -  Primary refractory multiple myeloma defined as participants who had never achieved at
             least a minimal response (MR) with any treatment during the disease course.

          -  Free Light Chain measurable disease only.

          -  Prior therapy with pomalidomide.

          -  Any anti-myeloma drug treatment within 14 days before randomization, including
             dexamethasone.

          -  Eastern Cooperative Oncology Group performance status superior to 2.

          -  Platelets inferior to 75 000 cells per microliter (mcL) if inferior to 50% of bone
             marrow (BM) nucleated cells are plasma cells, and inferior to 30 000 cells per mcL if
             superior or equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion
             was not allowed within three days before the screening visit.

          -  Absolute neutrophil count inferior to 1000 per mcL (1*10^9/L).

          -  Creatinine clearance inferior to 30 mL per minute (Modification of Diet in Renal
             Disease [MDRD] Formula).

          -  Total bilirubin superior to 2*ULN (Upper Limit of Normal).

          -  Corrected serum calcium superior to 14 milligrams per deciliter (mg/dL) (superior to
             3.5 millimoles per liter (mmol/L).

          -  Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) superior to
             3*ULN.

          -  Hypersensitivity to immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide)
             defined as any hypersensitivity reaction leading to stop IMiDs within the 2 first
             cycles or toxicity, which does meet intolerance definition.

          -  Hypersensitivity to dexamethasone, sucrose histidine (as base and hydrochloride salt),
             and polysorbate 80 or any of the components of study therapy that are not amenable to
             premedication with steroids, or H2 blockers that would prohibit further treatment with
             these agents.

          -  Significant cardiac dysfunction; myocardial infarction within 12 months; unstable,
             poorly controlled angina pectoris.

          -  Pregnant or breastfeeding woman or female who intends to become pregnant during the
             participation in the study.

          -  Male participants who disagreed to practice true abstinence or disagreed to use a
             condom during sexual contact with a pregnant female or a female of childbearing
             potential while participating in the study, during dose interruptions and at least 3
             or 5 months following study treatment discontinuation, even if he had undergone a
             successful vasectomy.

          -  All participants who disagreed to refrain from donating blood while on study treatment
             and for 4 weeks after discontinuation from this study treatment.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.