Isatuximab in Treating Patients With High Risk Smoldering Plasma Cell Myeloma

  • End date
    Jun 30, 2025
  • participants needed
  • sponsor
    M.D. Anderson Cancer Center
Updated on 14 May 2022
platelet count
multiple myeloma
monoclonal antibodies
bone marrow procedure
neutrophil count
monoclonal protein
growth factors
bone marrow plasma cells


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.



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.

Condition Smoldering Plasma Cell Myeloma
Treatment laboratory biomarker analysis, Methylprednisolone, Diphenhydramine, Phone Calls, Isatuximab, Ranitidine, Ranitidine
Clinical Study IdentifierNCT02960555
SponsorM.D. Anderson Cancer Center
Last Modified on14 May 2022


Yes No Not Sure

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)
>= 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)
criteria (patients must have at least 2 risk factors present)
of 2 risk factors: high risk for progression at a rate of 72% at 5 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) >= 1.0 x 10^9 /L
Creatinine clearance (CrCl) >= 40 ml/min; CrCl will be calculated using the
Hemoglobin more or equal than 2 grams/dL below the institutional level of normal
modification of diet in renal disease (MDRD) equation
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)
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
Bisphosphonates are permitted, including pamidronate, zoledronic acid, alendronate
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
ibandronate, risedronate
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
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