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

• Status: Recruiting
• Trial end date: 2028-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies the effect of isatuximab, carfilzomib, pomalidomide, and dexamethasone in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Isatuximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the proteins needed for cell growth. Chemotherapy drugs, such as pomalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving isatuximab, carfilzomib, pomalidomide, and dexamethasone may kill more cancer cells.

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

Details

• Lead Sponsor: University of Washington
• Collaborator: Genzyme, a Sanofi Company
• Treatments: Antibodies, Monoclonal; BB 1101; Dexamethasone; Dexamethasone acetate; Ichthammol; Pomalidomide

Criteria

Inclusion Criteria:

• Patients with relapsed or refractory multiple myeloma, with 1 to 3 therapies

• Must have received prior lenalidomide therapy and progressed on either a lenalidomide-containing regimen or lenalidomide maintenance (defined as a dose of 10-15 mg lenalidomide daily after induction regimen or maintenance)

• Must have measurable disease, as defined by International Myeloma Working Group criteria, having one or more of the following:

• Serum M protein >= 1.0 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 >= 2cm)

• 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 (with the exception of non-melanoma skin cancer, curatively treated localized prostate cancer, curatively treated superficial bladder cancer and cervical carcinoma in site on biopsy or a squamous intraepithelial lesion on papanicolaou [PAP] smear)

• Active hepatitis B, hepatitis C at time of screening

• Subjects with active uncontrolled infection

• Concurrent use of other anticancer agents or experimental treatments

• Treatment with anti-CD38 monoclonal antibody therapy in the last 6 months