LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies

Eligibility Criteria

• 1. Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential or plan to become pregnant during the study or within 1 month of the last dose of study treatment and women who are current lactating or plan to breastfeed during the study or within 1 week of the last dose of study treatment.
• 2. Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
• 1. HBV: Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before randomization. Patients who are hepatitis B PCR positive will be excluded.
• 2. Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA positive will be excluded.
• 3. Known active cytomegalovirus (CMV) infection (Unknown or negative status are eligible).
• 4. History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon requiring steroid therapy defined as \>20 mg of prednisone or equivalent daily.
• 5. Presence of ≥ grade 3 non-hematologic toxicities as per CTCAE version 5.0 from any previous treatment unless it is felt to be due to underlying disease.
• 6. Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution. Minimum of 14 days or 5 half-lives of the drug (whichever is shorter) washout prior to apheresis.
• 7. Refusal to participate in the long-term follow-up protocol.
• 8. Patients with active CNS involvement by malignancy on MRI or by lumbar puncture.
• 1. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was \>4 weeks before enrollment and a remission documented within 8 weeks of planned CAR-T cell infusion by MRI brain and CSF analysis.
• 9. Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are excluded if they are \<100 days post-transplant, have evidence of active graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.
• 10. Prior allogeneic CAR T-cell therapy \<100 days from prior CAR T-cell treatment.
• 11. Previous recipients of autologous CAR-T cell therapy directed at either cluster of differentiation 19 (CD19) or CD20 are excluded if they are \<100 days post prior CAR-T cell treatment (does not include re-enrollment) or have \>5% residual circulating CAR-T as measured by flow cytometry using a CD19 CAR detection reagent (Miltenyi Biotec).
• 12. Anti-CD20 antibody treatment within 4 weeks of cell infusion.
• 13. Anti-CD19 antibody treatment within 4 weeks of cell infusion.
• 14. Cytotoxic chemotherapy treatment within 14 days or steroid treatment (other than replacement dose steroids) within 7 days prior to apheresis collection for CAR-T cells.
• 15. No other oral chemotherapeutic agents or antibody directed treatment after starting pirtobrutinib other than steroids or radiation to a single site in a palliative fashion.
• 16. Patients post solid organ transplant who develop high grade lymphomas or leukemias.
• 17. Concurrent active malignancy other than basal or squamous cell carcinomas of the skin (underlying low-grade lymphoma chronic lymphocytic leukemia/Follicular lymphoma (FL) / Marginal zone lymphoma (MZL) is allowable in patients with transformed large cell lymphoma/Richter's.
• 18. Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor.
• 19. History of stroke or intracranial hemorrhage within 6 months of randomization.
• 20. Significant cardiovascular disease defined as myocardial infarction within 6 months of randomization, congestive heart failure with ejection fraction \<30%, active unstable angina, QT prolongation (QTcF)\>470 msec on ECG.
• 21. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug.
• 22. Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
• 23. Patients who had surgery within 4 weeks prior to randomization.
• 24. Patients who have received vaccination with live vaccine within 28 days prior to randomization.
• 25. Patients with known hypersensitivity to any of the excipients of pirtobrutinib.