This phase II trial tests how well bridging radiation therapy prior to axicabtagene ciloleucel (axi-cel) chimeric antigen receptor (CAR) T-cell therapy works in treating patients with diffuse large B-cell lymphoma that that has come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Bridging radiation therapy uses high energy x-rays or particles to kill pretreatment cancer cells. 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 (CAR). Large numbers of the CAR T-cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Information gained from this trial may allow researchers to determine whether bridging radiation therapy prior to axi-cel CAR T-cell therapy improves patient outcomes.
Additional locations may be listed on ClinicalTrials.gov for NCT06104592.
Locations matching your search criteria
United States
Florida
Tampa
Moffitt Cancer CenterStatus: Active
Contact: Michael David Jain
Phone: 813-745-4673
PRIMARY OBJECTIVES:
I. To investigate whether bridging radiotherapy prior to CAR T-cell therapy in large B-cell lymphoma patients with bulky disease, defined as any lesion ≥ 5cm, improves the 12-month progression-free survival (PFS) from 30% to 55% when compared to historical controls of high-risk patients who did not receive bridging radiation.
II. To assess safety, tolerability, and efficacy of bridging radiotherapy prior to CAR T-cell therapy in patients with diffuse large B-cell lymphoma (DLBCL) and its variants.
SECONDARY OBJECTIVES:
I. To investigate whether bridging radiotherapy prior to CAR T-cell therapy in high-risk patients, defined as at least one lesion ≥ 5cm, improves intention-to-treat (ITT) PFS and overall survival (OS) when compared historical cohort of high-risk patients who did not receive bridging radiation therapy.
II. To investigate whether bridging radiotherapy prior to CAR T-cell therapy alters the patterns of failure by changing the distribution and rates of local, distant, and combined relapses compared to the historical cohort described above.
III. To investigate whether bridging radiotherapy affects the rates and severity of cytokine release syndrome (CRS) and immune cell associated neurotoxicity syndrome (ICANS).
OUTLINE:
Patients undergo bridging radiation therapy (RT) every day (QD) or every other day (QOD) at the discretion of the treating radiation oncologist Monday-Friday for 5-15 fractions until day -5 in the absence of disease progression or unacceptable toxicity. After completion of bridging RT, patients receive lymphodepletion chemotherapy with fludarabine intravenously (IV) and cyclophosphamide IV QD on days -5 to -3 in the absence of unacceptable toxicity. Patients then receive axi-cel IV on day 0. Patients also undergo echocardiography (ECHO) during screening, as well as positron emission tomography (PET)/computed tomography (CT), CT, and blood sample collection throughout the trial. Patients may optionally undergo a biopsy during screening.
Upon completion of study treatment, patients are followed up on days 1, 3, 5, 7, 10, 12, 14, 17, 21, 30, 90, 180, and 365 and then months 18 and 24. Patients may be followed for 15 years for a long-term surveillance follow-up study.
Lead OrganizationMoffitt Cancer Center
Principal InvestigatorMichael David Jain
