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

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 63
• Participant gender: Both

Summary

The goal of this clinical research study is to learn if isatuximab can help to control smoldering multiple myeloma (SMM). The safety of this drug will also be studied.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Sanofi
• Treatments: Diphenhydramine; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Promethazine; Ranitidine; Ranitidine bismuth citrate
• Last Updated: 2016-11-08

Criteria

Inclusion Criteria:

1. Patients must have histologically confirmed SMM based on the following criteria: (A) MAYO CLINIC CRITERIA (patient must have at least 2 risk factors present) 1. Bone marrow core biopsy plasma cell involvement by CD138 immunohistochemistry >/= 10% 2. Monoclonal spike >/= 3g/dL 3 . Free light chain ratio in serum < 0.125 or > 8. *2 of 3 risk factors: intermediate risk for progression at a rate of 51% at 5 years *3 of 3 risk factors: high risk for progression at a rate of 76% at 5 years

2. OR (B) PETHEMA CRITERIA (patient must have at least 1 risk factor present) 1. >/=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) 2. Immunoparesis (This term refers to the patient having low uninvolved immunoglobulins in peripheral blood, for example if a patient has immunoglobulin A infantile genetic agranulocytosis (IgA) smoldering multiple myeloma, then either having a low immunoglobulin M (IgM) and/or low immunoglobulin G (IgG) will qualify as a risk factor for progression to multiple myeloma) *1 of 2 risk factors: intermediate risk for progression at a rate of 46% at 5 years *2 of 2 risk factors: high risk for progression at a rate of 72% at 5 years

3. OR (C) SWOG CRITERIA (patient must have 2 risk factors present or one risk factor if this risk factor if a GEP70 score of > -0.26) 1. Monoclonal spike >/= 3 g/dL 2. Involved free light chain >/= 25 mg/dL 3. GEP70 risk score > -0.26 (This risk score is calculated based on the expression of 70 genes after RNA extraction from CD138+ plasma cells in bone marrow aspirates) *>/=2 risk factors: high risk of progression at a rate of 70% at 2 years * We would also include patients with 1 risk factor as long as this risk factor is GEP70 risk score > -0.26 since patients with this risk factor have an intermediate risk of progression at a rate of 50% at 2 years.

4. Creatinine clearance (CrCl) >/= 50 ml/min. CrCl will be calculated using the Modification of Diet in Renal Disease (MDRD) equation.

5. Age >/= 18 years. Because no dosing or adverse event data are currently available on the use of Isatuximab in patients <18 years of age, children are excluded from this study.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

7. Absolute neutrophil count (ANC) >/=1.0 x 10^9 /L, hemoglobin >/= 11 g/dL and 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.

8. Adequate hepatic function, with bilirubin < 1.5 x the upper limit of normal (ULN), and AST and ALT < 3.0 x ULN.

9. 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 (eg, abstinence).

10. 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.

11. Subjects must be able to give informed consent

Exclusion Criteria:

1. Evidence of myeloma defining events or biomarkers of malignancy due to underlying plasma cell proliferative disorder meeting at least ONE of the following: 1. 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) 2. Renal Insufficiency: creatinine clearance < 50 ml/min or serum creatinine > 2 mg/dL 3. Anemia: hemoglobin value <10 g/dL or 2 g/dL < normal reference 4. 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) 5. Clonal bone marrow plasma cell percentage >/= 60% 6.Involved:uninvolved serum free light chain ratio >/=100 measured by Freelite assay (The Binding Site Group, Birmingham, UK) 7. > 1 focal lesions on MRI studies (each focal lesion must be 5 mm or more in size)

2. Prior or concurrent systemic treatment for SMM. b) Bisphosphonates are permitted, including pamidronate, zoledronic acid, alendronate, ibandronate, risedronate. c) 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. d) Radiotherapy is not permitted. e) Prior treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of multiple myeloma or cluster of differentiation 38 (CD38) drugs is not permitted.

3. Plasma cell leukemia

4. Pregnant or lactating females. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with isatuximab, breastfeeding should be discontinued if the mother is treated with isatuximab. These potential risks may also apply to other agents used in this study.

5. Active hepatitis B or C infection.* Known HIV infection* Intolerance to infused protein products, sucrose, histidine or polysorbate 80.* Concurrent treatment with other anti-cancer therapy is not permitted.

6. 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.

7. Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements

8. Contraindication to any concomitant medication, including pre-medications or hydration given prior to therapy

9. Major surgery within 1 month prior to enrollment