Isatuximab, Carfilzomib, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• Patients with relapsed or refractory multiple myeloma, with >= 1 prior therapy
• Must have received prior lenalidomide therapy
• Must have measurable disease, as defined by International Myeloma Working Group criteria, having one or more of the following: * Serum M protein >= 0.5 g/dL * Urine M protein >= 200 mg/24 hours * Involved serum free light chain level >= 10 mg/dL with abnormal kappa/lambda ratio * Measurable biopsy-proven plasmacytomas (>= 1 lesion has a single diameter >= 2 cm) * Bone marrow plasma cells >= 30%
• Age 18 years and older, and have the capacity to give informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Subjects should have resolution of any toxicities from prior therapy to grade =< 1 or baseline prior to enrollment (with the exception of peripheral neuropathy)
• Subjects are required to have grade =< 2 peripheral neuropathy to enroll
• Prior autologous stem cell transplant is allowed; patients must be >= 6 months post- autologous stem cell transplantation to enroll
• Estimated glomerular filtration rate (eGFR) >= 20 ml/min
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
• Total bilirubin =< 2 x ULN
• Absolute neutrophil count (ANC) >= 1,000/uL
• Platelets >= 50,000/uL
• Hemoglobin >= 8 g/dL
• Growth factor use or transfusions may be used to meet the eligibility requirement for ANC, platelets, and hemoglobin
• Female patients of childbearing potential and male patients must agree to use 2 effective forms of contraception or continuously abstain from heterosexual intercourse during the period of therapy, and for 6 months after discontinuation of study treatment for females and 3 months after discontinuation of study treatment for males

Exclusion Criteria

• History of clinically significant cardiovascular disease, including congestive heart failure New York Heart Association (NYHA) class 3-4, symptomatic ischemia, left ventricular ejection fraction < 40%, uncontrolled conduction abnormalities, myocardial infarction in last 6 months
• Uncontrolled hypertension as determined by the principal investigator (PI) or designee
• Active plasma cell leukemia or systemic amyloid light-chain (AL) amyloidosis
• History of another primary malignancy that has not been in remission for at least 1 year * However, the following diagnoses are eligible for inclusion: non-melanoma skin cancer, localized prostate cancer, superficial bladder cancer, cervical carcinoma in situ, on biopsy or any prior malignancy with an estimated > 90% 1-year cure rate per sponsor-investigator
• For patients with chronic hepatitis B viral infection, the hepatitis B virus (HBV) polymerase chain reaction (PCR) must be undetectable on suppressive therapy
• Patients with a history of Hepatitis C viral infection must have been treated and cured. For patients on treatment for hepatitis C, they are eligible if they have an undetectable hepatitis C virus (HCV) viral load
• Subjects with active uncontrolled infection
• Concurrent use of other anticancer agents or experimental treatments