This is a phase 2, open-label, randomized, multicenter clinical trial in patients with relapsed/refractory mantle cell lymphoma (R/R MCL) who meet the criteria for standard-of-care FDA label for CD19 CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel).
Patients with a histologically confirmed diagnosis of mantle cell lymphoma (MCL) will be eligible.
Adult males or females who are 18 years of age or older at time of signing informed consent.
Must have ability to comprehend and the willingness to sign written informed consent for study participation.
Eligible to receive CAR T-cell therapy (Brexucabtagene autoleucel) for MCL by the standard of care label, which states: "TECARTUS or Brexucabtagene autoleucel is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL)"
Patients who have previously received treatment with pirtobrutinib for >2 months prior to study enrollment are ineligible. Patients who are relapsed or refractory and then received less than 2 months of pirtobrutinib as "holding therapy" while awaiting CAR T-cell therapy evaluation, and who did not demonstrate disease progression while on pirtobrutinib holding therapy, are eligible.
Patients who have previously discontinued pirtobrutinib due to disease progression, intolerance, or toxicity.
Patients who are currently receiving or who have received any investigational study agent ≤4 weeks prior to screening visit are ineligible.
Prior treatment with chimeric antigen receptor (CAR) T-cell therapy.
Parallel
Pirtobrutinib
DrugPirtobrutinib is a non-covalent BTKi that has preserved activity in the presence of mutations that drive BTKi resistance.
Brexucabtagene Autoleucel
DrugBrexucabtagene autoleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy (brexu-cel).
Progression-free survival (PFS) - Historical comparison
The one-sample log-rank test will be used to determine if there's a statistically significant difference in PFS in patients treated on this trial of pirto plus brexucel compared to a historical control.
Progression-free survival (PFS) - Comparison between arm A and arm B
The one-sample log-rank test will be used to determine if there's a statistically significant difference in PFS in patients treated with concurrent pirtobrutinib ("con-pirto") versus patients treated with no concurrent pirtobrutinib ("con-none").
Severe ICANS
Number of participants experiencing severe ICANS (grade 3 or higher by ASTCT criteria) in the first 60 days after CAR T infusion.
Severe CRS
Number of participants experiencing severe CRS (grade 3 or higher by ASTCT criteria) in the first 60 days after CAR T infusion.
Overall Response Rate (ORR)
Best Overall Response Rate (ORR) by Lugano Criteria in the full cohort compared to the historical control, and comparing between Arm A and Arm B.
Overall survival (OS)
Overall survival (OS) of patients treated with pirtobrutinib with brexu-cel in the full cohort compared to the historical control, and comparing between Arm A and Arm B.
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H. Lee Moffitt Cancer Center and Research Institute
Lead sponsor
Bankhead-Coley Florida Biomedical Research Program
Collaborator
Eli Lilly and Company
Collaborator
