Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients

Overview

About this study

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 patients 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 Progression Free Survival (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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria :

  • Age superior or equal to 18 years or country's legal age of majority if the legal age is superior to 18 years old.
  • Patients must have a documented diagnosis of multiple myeloma with evidence of measurable disease i.e. serum M protein superior or equal to 0.5 g per 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.
  • Patients must have 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.
  • Patients must have failed treatment with lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination.
  • Patients must have 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 patients who have 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 µL if inferior to 50% of bone marrow (BM) nucleated cells are plasma cells, and inferior to 30 000 cells per µL if superior or equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within three days before the screening visit.
  • Absolute neutrophils count inferior to 1000 per μL (1 x 10E9/L). The use of G-CSF is not allowed to reach this level.
  • Creatinine clearance inferior to 30 mL per min (MDRD Formula).
  • Total bilirubin superior to 2 x ULN (Upper Limit of Normal).
  • Corrected serum calcium superior to 14 mg per dL (superior to 3.5 mmol per L).
  • Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) superior to 3 x ULN.
  • Hypersensitivity to 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 disagree to practice true abstinence or disagree 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 months following study treatment discontinuation, even if he has undergone a successful vasectomy.
  • All patients who disagree to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment.

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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Joseph Mikhael, M.D.

Closed for enrollment

Contact information:

Research Information Center

800-664-4542

Rochester, Minn.

Mayo Clinic principal investigator

Joseph Mikhael, M.D.

Closed for enrollment

Contact information:

Research Information Center

800-664-4542

More information

Publications

  • Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. Read More on PubMed
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CLS-20323763

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