Phase 2 Study of Pirtobrutinib and Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma

Inclusion Criteria

• Must have a confirmed diagnosis of mantle cell lymphoma (MCL).
• Be 18 years or older.
• Able to understand and sign a consent form.
• Eligible for CAR T-cell therapy (Brexucabtagene Autoleucel) as per standard guidelines.
• Have a performance status score of 0 to 2, indicating full activity or some restriction in strenuous activities.
• Must have stopped certain previous cancer treatments for a specified time before starting the study:
  • Targeted agents or chemotherapy: 5 half-lives or 2 weeks, whichever is shorter.
  • Antibody-drug conjugates: 10 weeks.
  • Radiation therapy: 14 days for broad field, 7 days for limited field.
  • Bendamustine or similar drugs: 3 months.
  • Corticosteroids: 5 days.
• Women and men must agree to use effective birth control during the study and for a specified time after.
• Women of childbearing potential must have a negative pregnancy test before starting the study.
• Must meet certain blood and organ function criteria:
  • Platelets, hemoglobin, and neutrophil counts above specified levels.
  • Liver and kidney function within specified limits.
  • Heart function with an ejection fraction of at least 40%.
  • Adequate lung function and blood clotting ability.

Exclusion Criteria

• Previously treated with Pirtobrutinib for more than 2 months before the study.
• Previously stopped Pirtobrutinib due to disease progression or side effects.
• Received any investigational drug within 4 weeks before the study.
• Prior treatment with CAR T-cell therapy.
• Significant heart disease or arrhythmias.
• Active or uncontrolled infections.
• Active autoimmune or inflammatory diseases affecting the brain.
• Active involvement of mantle cell lymphoma in the brain.
• Positive for HIV, hepatitis B, or hepatitis C unless under control.
• Need for chronic steroids or immunosuppressants.
• Allergic to Pirtobrutinib or similar drugs.
• Not recovered from side effects of previous cancer treatments.
• Pregnant or breastfeeding women.
• Conditions that interfere with study participation or drug absorption.
• History of major bleeding or heart arrhythmias with previous treatments.
• Major surgery within 4 weeks before the study.
• History of bleeding disorders.
• Need for blood thinners like warfarin.
• Active second cancer unless in remission with a life expectancy over 2 years.
• Recent vaccination with live vaccines.
• History of stroke or brain bleeding within 6 months.
• Recent stem cell transplant with complications.
• Uncontrolled autoimmune blood disorders.