DART: Phase II Study of Dasatinib and Quercetin in Patients With Relapsed, Refractory Multiple Myeloma Receiving CAR-T Therapy
This phase II trial tests how well giving dasatinib and quercetin with cyclophosphamide, fludarabine and chimeric antigen receptor (CAR)-T cell therapy works in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Quercetin is a compound found in plants that may prevent multiple myeloma from forming. Chemotherapy such as cyclophosphamide and fludarabine are given to help kill any remaining cancer cells in the body and to prepare the bone marrow for CAR-T therapy. Chimeric antigen receptor T-cell Therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving dasatinib and quercetin with cyclophosphamide, fludarabine and CAR-T cell therapy may kill more cancer cells in patients with relapsed or refractory multiple myeloma.
• Age ≥ 18 years
• Relapsed or refractory multiple myeloma who has had at least 3 prior lines of therapies including a proteasome inhibitor, immunomodulatory drug (IMiD) and anti-CD38 monoclonal antibody (mAb)
• Ciltacabtagene autoleucel (Carvykti) available for patient
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Life expectancy ≥ 12 weeks
• Hemoglobin ≥ 8.0 g/dL (obtained ≤ 14 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 (obtained ≤ 14 days prior to registration)
• Platelet count ≥ 50,000/mm\^3 (obtained ≤ 14 days prior to registration)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration)
⁃ Note: Patients with Gilbert's syndrome must have a total bilirubin of ≤ 3 x ULN (obtained ≤ 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2 x ULN (obtained ≤ 14 days prior to registration)
• Alkaline phosphatase ≤ 1.5 x ULN (obtained ≤ 14 days prior to registration)
• Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault formula (obtained ≤ 14 days prior to registration)
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only
⁃ Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry and for the duration of study participation and for at least 30 days after the last dose of study drug
• Provide written informed consent
• Willingness to provide mandatory blood and bone marrow specimens for correlative research
• Willingness to provide mandatory bone marrow cores and/or tissue specimens for correlative research
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)