A Study of Venetoclax in Combination With Isatuximab and Dexamethasone for Relapsed/Refractory Multiple Myeloma

Inclusion Criteria

• •1.Has a diagnosis of MM based on standard criteria as follows: Myeloma Criteria: Must be At least 1 of 2
• •1. Clonal bone marrow plasma cells \>10%
• •2. Biopsy-proven bony or extramedullary plasmacytoma
• •Active Myeloma criteria: Must Meet At Least ONE of the Following:
• •Meet at least one of the sub-criteria for #1 Evidence of End Organ Damage (a, b, c, or d), OR Meet sub-criteria #2. 60% or greater bone marrow plasma cells, OR Meet sub-criteria #3 Serum free light chain ratio, OR Meet sub-criteria #4 More than one focal lesion on MRI \> 5mm in size.
• •1. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically
• •1. Hypercalcemia: serum calcium \>0.25 mmol/L (\>1mg/dL) higher than the upper limit of normal or \>2.75 mmol/L (\>11mg/dL)
• •2. Renal insufficiency: creatinine clearance \<40 mL per minute or serum creatinine \>177mol/L (\>2mg/dL)
• •3. Anemia: hemoglobin value of \>20g/L below the lowest limit of normal, or a hemoglobin value \<100g/L
• •4. Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET/CT. If bone marrow has \<10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement
• •2. 60% or greater clonal plasma cells on bone marrow examination
• •3. Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg/L (a patient's involved free light chain either kappa or lambda is the one that is above the normal reference range; the uninvolved free light chain is the one that is typically in, or below, the normal range)
• •4. More than one focal lesion on MRI that is at least 5mm or greater in size The patient must have met the criteria for Active Myeloma at some stage following the diagnosis of Myeloma. Source documentation for both Myeloma and Active Myeloma will be required.
• •2\. Currently has MM with measurable disease, defined as:
• •1. a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or urine monoclonal protein levels of at least 200 mg/24 hours
• •2. for patients without measurable serum and urine M-protein levels, an involved SFLC \> 100 mg/L or abnormal SFLC ratio
• •3. for patients with IgD MM, a monoclonal immunoglobulin IgD of at least 1500 mg/L or meet other measurable disease eligibility criteria
• •3\. Show the (11;14), as demonstrated by FISH or cytogenetic analysis at screening or at any point prior to screening. If performed more than 45 days prior, it should be repeated at the investigator's discretion.
• •4\. Absolute neutrophil count ≥ 1.5 x 109/L 5. Platelet count ≥ 75 x 109/L 6. Hemoglobin ≥ 8.0 g/dL within 21 days prior to enrollment. 7. Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute as calculated by Cockcroft-Gault method 8. Total bilirubin levels ≤ 2.0 mg/dL (normal levels) 9. AST (SGOT) and ALT (SGPT) ≤ 2 x ULN 10. Serum potassium 3.0-5.5 mEq/L 11. Female of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts taking treatment drugs. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Contraception measures should be continued for 3 months following the treatment completion.
• •†A FCBP (female of childbearing potential) is a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months 12. Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 2 13. Participant must have received at least 1 prior line of therapy for multiple myeloma, including a proteasome inhibitor, lenalidomide, and glucocorticosteroids but not necessarily in one treatment regimen 14. Participant currently has documented progressive MM per IMWG criteria