Testing Drug Treatments After CAR T-cell Therapy in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

Description

PRIMARY OBJECTIVES:

I. To compare the progression-free survival in participants with relapsed/refractory large B-cell lymphoma or follicular lymphoma grade 3B with stable disease (SD) or partial remission (PR) on first imaging response by central review (day +30 positron emission tomography [PET]/computed tomography [CT] scan) after commercial CD19 CAR T-cell therapy who are randomized to receive each consolidation therapy versus those that receive no consolidation therapy (i.e. control).

Ia. Specifically, to compare the progression free survival (PFS) of 1) mosunetuzumab consolidation to no consolidation, 2) polatuzumab vedotin consolidation to no consolidation, 3) mosunetuzumab + polatuzumab vedotin to no consolidation.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) in participants randomized to each consolidation treatment arm versus control.

II. To compare the complete remission (CR) conversion rate up to one year in participants randomized to each consolidation arm versus control.

III. To evaluate the treatment-related adverse events in participants randomized to each consolidation arm.

IV. To evaluate the association between total metabolic tumor volume (TMTV), standardized uptake value (SUV) max, and sum product (SPD) of diameters by PET-CT at first imaging response with complete remission conversion up to one year in participants randomized to each consolidation arm as well as those randomized to control.

V. To evaluate the overall response rate (ORR), CR rate, PFS, and OS of participants randomized to Arm 4 (observation) who have lymphoma progression within 12 months of CAR T-cell infusion and subsequently ‘cross-over’ to receive treatment with mosunetuzumab + polatuzumab vedotin.

VI. To estimate overall survival for all patients registered to this study. VII. To assess the difference in overall survival between participants who achieved CR at first imaging (day +30) versus those who did not achieve CR at first imaging.

BANKING OBJECTIVES:

I. To bank specimens for future correlative studies. II. To bank PET-CT images for future correlative studies.

OUTLINE:

STEP I: Patients receive lymphodepleting chemotherapy consisting of fludarabine intravenously (IV) and cyclophosphamide IV on study. Patients then receive tisagenlecleucel IV, axicabtagene ciloleucel IV, or lisocabtagene maraleucel IV on study.

STEP II: Patients are randomized to 1 of 4 arms.

ARM I: Patients receive mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

ARM II: Patients receive polatuzumab vedotin IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

ARM III: Patients receive polatuzumab vedotin IV and mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

ARM IV: Patients undergo observation on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study. Patients with subsequent progression within 12 months of CAR T-cell therapy may crossover to Arm III.