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.
Additional locations may be listed on ClinicalTrials.gov for NCT06940297.
Locations matching your search criteria
United States
Minnesota
Rochester
Mayo Clinic in RochesterStatus: Active
Contact: Yi Lin
Phone: 507-284-2511
PRIMARY OBJECTIVE:
I. Assess the rate of bone marrow minimal residual disease (MRD) negativity and positron emission tomography (PET)/computed tomography (CT) MRD negativity at month 3 post CAR-T infusion.
SECONDARY OBJECTIVES:
I. Assess the overall response rate (ORR), partial response (PR), very good partial response (VGPR), complete response (CR)/stringent complete response (sCR).
II. Assess the duration of response (DOR) and progression free survival (PFS).
III. Assess the safety of combination dasatinib and quercetin (D+Q) with CAR-T.
IIIa. Assess the rate, severity and duration of cytokine release syndrome;
IIIb. Assess the rate, severity and duration of Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS);
IIIc. Assess cytopenia in the first 12 months post CAR-T;
IIId. Assess the rate, severity and duration of late-onset neurologic symptoms including cranial nerve palsies and neurocognitive movement disorders.
CORRELATIVE OBJECTIVES:
I. Assess the percent of myeloma cells dormant state in the bone marrow or plasmacytoma prior to CAR-T therapy.
II. Quantify changes in the percent of myeloma cells in dormant state in the bone marrow or plasmacytoma 1 day after CAR-T therapy.
OUTLINE:
Patients receive dasatinib orally (PO) once daily (QD) and quercetin PO twice daily (BID) on days -7 and -6 and cyclophosphamide intravenously (IV) over 60 minutes and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients then receive CAR-T IV on day 0. Patients receive dasatinib PO QD and quercetin PO BID on days 28, 29, 58, 59, 88 and 89 in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and/or PET, tumor biopsy, bone marrow aspirate and biopsy and blood and collection throughout the study.
After completion of study treatment, patients are followed up at progression, at 30 days and every 3 months for 24 months.
Lead OrganizationMayo Clinic in Rochester
Principal InvestigatorYi Lin