This early phase I trial tests the safety and tolerability of adding vancomycin to radiation as bridging therapy in patients undergoing chimeric antigen receptor T-cell (CART) therapy for B-cell lymphoma. Most patients who receive CART cells will need to receive some type of anticancer therapy between the time that their T cells are removed from their bodies (a procedure called leukapheresis) and when the CART cells are put back into their bodies. This anti-cancer therapy is called “bridging therapy”. Bridging therapy is important because reducing the amount of lymphoma prior to T cell infusion makes CART cells more effective and safer. When lymphoma is under better control prior to CART cell infusion, the CART cells are more likely to effectively treat lymphoma long term. Radiation treats B cell lymphoma well and radiation therapy is often used as a bridging therapy before CART infusion. Research suggests that the bacterial makeup in the gut may play a role in enhancing the body’s immune response and improving outcomes after cancer treatment. Oral vancomycin, a Food and Drug Administration-approved antibiotic taken by mouth, is typically used to treat a gut infection called Clostridium difficile. It is also believed to change the overall makeup of the intestinal bacteria. Taking vancomycin before, during, and after radiation and CART cell therapy may help radiation and CART cells work better in patients with B-cell lymphoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07478848.
Locations matching your search criteria
United States
Pennsylvania
Philadelphia
University of Pennsylvania/Abramson Cancer CenterStatus: Active
Contact: Elise A. Chong
Phone: 215-615-5858
PRIMARY OBJECTIVE:
I. To assess the safety and tolerability of bridging radiation therapy (RT) with vancomycin prior to CART therapy.
SECONDARY OBJECTIVES:
I. To assess the efficacy of bridging RT with vancomycin prior to CART therapy.
II. To evaluate the gut microbiome composition and impact on efficacy.
EXPLORATORY OBJECTIVES:
I. To assess molecular pathways associated with improved complete response (CR) rates.
II. To assess metabolic pathways associated with vancomycin administration.
III. To determine stool metabolites, such as short chain fatty acid (SCFA) concentration, that are affected by vancomycin and correlated with response to CART.
IV. To identify additional roles played by bacterial macrovesicle in the synergy between RT, vancomycin, and CART.
V. To immune profile the lymphocyte population in peripheral blood mononuclear cells (PBMCs) and tumor infiltrate.
OUTLINE:
Patients receive vancomycin orally (PO) four times daily (QID) for 1 week prior to RT, for the duration of RT, and up to 2 weeks after CAR-T infusion, for a total of approximately 5 weeks. Patients undergo RT for 2-5 fractions prior to CAR-T infusion, between days -15 and -7. Following RT, patients receive standard of care (SOC) lymphodepletion chemotherapy between days -3 and -1 and undergo SOC CAR-T infusion on day 0. Patients also undergo leukapheresis on study and undergo collection of blood samples and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) and/or CT throughout the trial.
After completion of study treatment, patients are followed up on days 7, 14, 28-35, 90-120, and then every 3 months for 12 months.
Lead OrganizationUniversity of Pennsylvania/Abramson Cancer Center
Principal InvestigatorElise A. Chong
