This phase I trial tests the safety, side effects, and best dose of LMY-920 in treating patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). LMY-920 is a type of chimeric antigen receptor (CAR) T-cell therapy. CAR 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. Patients in this study also receive obinutuzumab prior to T-cell collection and cyclophosphamide and fludarabine before LMY-920 infusion. Obinutuzumab is a monoclonal antibody that may help control the disease and may decrease the number of CLL/SLL cells in the bloodstream, which may improve the quality of the CAR T-cells. Chemotherapy drugs such as cyclophosphamide and fludarabine are given before CAR T-cell infusions to prepare the body to receive the CAR T-cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell’s deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body’s immune response. Fludarabine injection is in a class of medications called purine analogs. It works by slowing or stopping the growth of cancer cells in the body. LMY-920 may be a safe treatment option for patients with relapsed or refractory CLL/SLL.
Additional locations may be listed on ClinicalTrials.gov for NCT06916767.
Locations matching your search criteria
United States
Ohio
Cleveland
Case Comprehensive Cancer CenterStatus: Active
Contact: Paolo Fabrizio Caimi
Phone: 216-445-4635
PRIMARY OBJECTIVE:
I. To determine recommended phase II dose of human autologous BAFF-expressing CAR T cells LMY-920 (LMY-920) in patients with relapsed or refractory CLL/SLL.
SECONDARY OBJECTIVES:
I. To establish toxicity profile for the infusion of LMY-920.
II. To determine the objective response rate per International Workshop in Chronic Lymphocytic Leukemia after treatment with LMY-920 in patients with relapsed or refractory CLL/SLL.
III. To determine the complete response rate per International Workshop in Chronic Lymphocytic Leukemia after treatment with LMY-920 in patients with relapsed or refractory CLL/SLL.
IV. To determine the duration of response in patients with relapsed or refractory CLL/SLL treated with LMY-920.
V. To determine the progression-free survival in patients with relapsed or refractory CLL/SLL lymphoma treated with LMY-920.
VI. To determine the overall survival in patients with relapsed or refractory CLL/SLL treated with LMY-920.
VII. To determine incidence of adverse events (AE) in patients with relapsed or refractory CLL/SLL treated with LMY-920.
VIII. To determine incidence of anti- LMY-920 antibodies in patients with relapsed or refractory CLL/SLL treated with LMY-920.
CORRELATIVE OBJECTIVES:
I. To describe the persistence of BAFF CAR-T cells as measured by flow cytometry and/or quantitative polymerase chain reaction (qPCR).
II. To measure changes in serum concentration of cytokines, T cell proteomics (polyfunctional index by IsoLight), and their effect on response (complete or partial response), and changes in LMY-920 cell subpopulations over time.
III. To measure expression of BR3, TACI, and BCMA on lymphoma cells and their associations with response.
IV. To measure changes in soluble levels of BR3, TACI, and BCMA and their associations with response.
V. To measure development of anti-LMY-920 antibodies.
VI. To measure T cell and myeloid cell activity.
VII. To measure circulating tumor DNA and its correlation with disease response.
VIII. To measure the effect of pre-apheresis B cell depletion with obinutuzumab on circulating cytokines.
IX. To measure the effect of pre-apheresis B cell depletion with obinutuzumab on T cell populations at the time of apheresis and on the final CAR T-cell product.
OUTLINE: This is a dose escalation study of LMY-920 in combination with obinutuzumab, cyclophosphamide, and fludarabine.
Patients receive obinutuzumab intravenously (IV) on two consecutive days and then undergo collection of peripheral blood mononuclear cells (PBMCs) 14-21 days later for manufacturing of the LMY-920 product. Patients receive cyclophosphamide IV over 60 minutes and fludarabine IV over 30 minutes on days -5 to -3, followed by LMY-920 IV over 5-30 minutes on day 0. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and undergo collection of blood samples, computed tomography (CT) or positron emission tomography (PET)/CT, and bone marrow biopsy and aspiration throughout the study.
After completion of study treatment, patients are followed up on days 1-7, 14, 21, 28, 60, and 90, at 6 and 12 months, and then annually in years 2-15.
Lead OrganizationCase Comprehensive Cancer Center
Principal InvestigatorPaolo Fabrizio Caimi