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Isatuximab in Treating Patients With High Risk Smoldering Plasma Cell Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02960555
Recruitment Status : Recruiting
First Posted : November 9, 2016
Last Update Posted : April 26, 2022
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well isatuximab works in treating patients with high risk smoldering plasma cell myeloma. Immunotherapy with monoclonal antibodies, such as isatuximab, may induce changes in the body's immune system and may interfere with the ability of the tumor cells to grow and spread.

Condition or disease Intervention/treatment Phase
Smoldering Plasma Cell Myeloma Biological: Isatuximab Other: Laboratory Biomarker Analysis Phase 2

Detailed Description:


I. To determine the rate of response according to the International Myeloma Working Group Criteria.


I. To determine progression free survival (PFS) at 2 years. II. To determine overall survival (OS). III. To determine duration of response (DOR). IV. To determine the clinical benefit rate (CBR). V. To evaluate safety of single agent treatment in this population. VI. To evaluate the immunogenicity of isatuximab.


Patients receive isatuximab intravenously (IV) over 5 hours on day 1 of cycle 1, and over 3 hours thereafter on days 8, 15, and 22 of cycle 1, on days 1 and 15 of cycles 2-6, and on day 1 of subsequent cycles. Treatment repeats every 28 days for up to 30 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Single Arm Trial of Isatuximab (SAR650984) in Patients With High Risk Smoldering Multiple Myeloma
Actual Study Start Date : February 8, 2017
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Isatuximab

Arm Intervention/treatment
Experimental: Treatment (isatuximab)
Patients receive isatuximab IV over 5 hours on day 1 of cycle 1, and over 3 hours thereafter on days 8, 15, and 22 of cycle 1, on days 1 and 15 of cycles 2-6, and on day 1 of subsequent cycles. Treatment repeats every 28 days for up to 30 cycles in the absence of disease progression or unacceptable toxicity.
Biological: Isatuximab
Given IV
Other Names:
  • Hu 38SB19
  • Isatuximab-irfc
  • SAR 650984
  • SAR650984
  • Sarclisa

Other: Laboratory Biomarker Analysis
Correlative studies

Primary Outcome Measures :
  1. Overall response (>= partial response) [ Time Frame: 6 months ]
    The trial will be conducted by the Simon's optimal two-stage design and the response rate will be estimated accordingly. Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the adverse event rate.

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 2 years ]
    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

  2. Overall survival [ Time Frame: Up to 5 years ]
    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

  3. Incidence of adverse events [ Time Frame: Up to 5 years ]
    Adverse events will be summarized by frequency tables for all patients. For the safety endpoint, per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.

Other Outcome Measures:
  1. Rate of minimal residual disease (MRD) negativity at complete remission assessed by flow cytometry and next generation sequencing [ Time Frame: Up to 2 years ]
    MRD assessed will be based on bone marrow aspirates. Will use 8-color flow cytometry as well as next generation sequencing of the variable (V) diversity (D) joining (J) segment.

  2. Molecular profiling [ Time Frame: Baseline up to progression of disease, assessed up to 5 years ]
    Will include whole exome sequencing and gene expression profiling and cellular (including flow cytometry) profiling using bone marrow aspirate samples.

  3. Immune characterization [ Time Frame: Baseline up to 2 years ]
    Cell surface and functional studies of dendritic, T-, B-, natural killer (NK)- and NKT-cells using bone marrow aspirate samples and peripheral blood samples.

  4. Mechanisms of resistance to isatuximab [ Time Frame: Up to 5 years ]
    Will include generation of isatuximab resistant myeloma cells, gene expression profiling in drug-naive and resistant myeloma cells, identification of molecular pathways involved in the generation of the resistant phenotype and mechanisms of dual resistance to isatuximab and other myeloma drugs.

  5. Genetic polymorphisms [ Time Frame: Baseline ]
    Will include FcGR genetic variations assessed using peripheral blood samples.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have histologically confirmed smoldering multiple myeloma (SMM) based on the following criteria; both criteria must be met:

    • 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%
    • Absence of myeloma defining events or amyloidosis
  • Additionally, patients must meet criteria for high risk of progression to multiple myeloma by Programa para el Tratamiento de Hemopatias Malignas (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02960555

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Contact: Shawnee Carpenter 713-563-8210

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United States, New York
Mount Sinai Hospital Recruiting
New York, New York, United States, 10029
Contact: Sundar Jagannath    212-241-7873      
Principal Investigator: Sundar Jagannath         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Carl O. Landgren    212-639-5153      
Principal Investigator: Carl O. Landgren         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Shawnee Carpenter    713-563-8210   
Principal Investigator: Elisabet E. Manasanch         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Elisabet E Manasanch M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT02960555    
Other Study ID Numbers: 2015-0148
NCI-2016-01922 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0148 ( Other Identifier: M D Anderson Cancer Center )
First Posted: November 9, 2016    Key Record Dates
Last Update Posted: April 26, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs