Trial of Isatuximab (SAR650984) in Patients With Intermediate and High Risk Smoldering Multiple Myeloma

What's the purpose of this trial?

This phase II trial studies how well isatuximab works in treating patients with high risk smoldering plasma cell myeloma.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Patients must have histologically confirmed smoldering multiple myeloma (SMM) based on the following criteria; both criteria must be met: (a) serum monoclonal protein (IgG or IgA) >= 3 g/dL or urinary monoclonal protein >= 500 mg per 24 hours and/or clonal bone marrow plasma cells 10-60% (b) absence of myeloma defining events or amyloidosis
  • Additionally, patients must meet criteria for high risk of progression to multiple myeloma by PETHEMA CRITERIA (patients must have at least 2 risk factors present)
    • >= 95% abnormal plasma cells/total plasma cells in bone marrow compartment (this is measured as a percentage of the total abnormal versus normal plasma cells in the bone marrow compartment using standard flow cytometry of the bone marrow aspirate; having >= 95% abnormal plasma cells/total plasma cells constitutes a risk factor for progression to multiple myeloma by PETHEMA criteria)
    • Immunoparesis (this term refers to the patient having low uninvolved immunoglobulins in peripheral blood, for example if a patient has IgA smoldering multiple myeloma, then either having a low IgM and/or low IgG will qualify as a risk factor for progression to multiple myeloma)
      • 2 of 2 risk factors: high risk for progression at a rate of 72% at 5 years
  • Creatinine clearance (CrCl) >= 40 ml/min; CrCl will be calculated using the modification of diet in renal disease (MDRD) equation
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1.0 x 10^9 /L
  • Hemoglobin more or equal than 2 grams/dL below the institutional level of normal
  • Platelet count >= 90 x 10^9/L
  • Platelet and blood transfusions are allowed on protocol; growth factors, including granulocyte colony stimulating factors and erythropoietin are allowed
  • Bilirubin < 1.5 x the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x ULN
  • Females of childbearing potential and male subjects with female partners of childbearing potential must agree to avoid pregnancy by using an adequate method of contraception (2 barrier method or 1 barrier method with a spermicide or intrauterine device for 2 weeks prior to screening, during and 12 weeks after the last dose of trial medication; adequate methods of contraception are provided as examples; other acceptable and effective methods of birth control are also permitted (e.g., abstinence)
  • Men must agree to not donate sperm while on the study and for at least 3 months after the last dose of study drug(s); women of child bearing potential must have a negative serum pregnancy test result within 7 days prior to the first administration of isatuximab and at the end of treatment visit; a negative urine pregnancy test is required prior to each subsequent isatuximab dose administration
  • Subjects must be able to give informed consent

Exclusion Criteria:

  • Evidence of myeloma defining events or biomarkers of malignancy due to underlying plasma cell proliferative disorder meeting at least ONE of the following:
    • Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL)
    • Renal insufficiency: creatinine clearance < 50 ml/min or serum creatinine > 2 mg/dL
    • Anemia: hemoglobin value < 10 g/dL or 2 g/dL < normal reference
    • Bone lesions: one or more osteolytic lesions on skeletal radiography, computerized tomography (CT) or 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography CT (PET-CT)
    • Clonal bone marrow plasma cell percentage >= 60%
    • Involved: uninvolved serum free light chain ratio >= 100 measured by freelite assay
    • > 1 focal lesions on magnetic resonance imaging (MRI) studies (each focal lesion must be 5 mm or more in size)
  • Bisphosphonates are permitted, including pamidronate, zoledronic acid, alendronate, ibandronate, risedronate.
  • Treatment with corticosteroids is not permitted, unless the patient is on a stable chronic dose of inhaled steroids to treat respiratory diseases or on stable chronic steroid replacement therapy for endocrinology disorders.
  • Radiotherapy is not permitted.
  • Prior or concurrent treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of multiple myeloma or CD38 drugs is not permitted.
  • Plasma cell leukemia
  • Pregnant or lactating females; breastfeeding should be discontinued if the mother is treated with isatuximab; these potential risks may also apply to other agents used in this study.
  • Active hepatitis B or C infection
  • Known human immunodeficiency virus (HIV) infection
  • Intolerance to infused protein products, sucrose, histidine or polysorbate 80
  • Concurrent treatment with other anti-cancer therapy is not permitted
  • Has significant cardiovascular disease with New York Heart Association (NYHA) class III or IV symptoms, or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination
  • Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements
  • Contraindication to any concomitant medication, including pre-medications or hydration given prior to therapy
  • Major surgery within 1 month prior to enrollment
  • Patients with pre-existing uncontrolled pulmonary disease will be excluded; uncontrolled refers to patients having had at least one hospitalization due to pulmonary disease (for example, asthma, chronic obstructive pulmonary disease) within the 6 months prior to enrollment in the study; patients with previous history of pneumonitis will be excluded

Additional Trial Information

Phase 2

Enrollment: 61 patients (estimated)

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

New York

Memorial Sloan Kettering Cancer Center

New York, NY

Open and Accepting

Mount Sinai Hospital Tisch Cancer Institute

New York, NY

Open and Accepting


MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting
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