Modified Immune Cells (CD19 CAR T Cells) and Acalabrutinib for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

Exclusion Criteria

• •1. Allogeneic hematopoietic cell transplantation (HCT) within the last 6 months.
• •2. Autologous HCT within the last 3 months.
• •3. Prior failure of any BTK inhibitor therapy. (Participant WILL be allowed if, after administration of other BTK inhibitors they have switched to acalabrutinib prior to lymphodepletion, and if the duration of all BTK inhibitor therapy was ≤ 3-7 months).
• •4. Participants known to have mutations associated with resistance to BTK inhibitors from prior studies.
• •Concomitant therapies
• •5. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (i.e., prednisone ≤ 7.5 mg /day, or hydrocortisone ≤ 20 mg /day) is allowed. During study participation, participants may receive systemic corticosteroids as needed for treatment-emergent comorbid conditions.
• •6. Approved anti-cancer therapies other than acalabrutinib are not allowed after enrollment, with the exception of steroids or involved field radiation to control progressive disease during cell manufacturing, prior to lymphodepletion/start of protocol therapy.
• •7. Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
• •8. Unable to discontinue anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of leukapheresis and remain off through end of study treatment.
• •Other illnesses or conditions
• •9. Class III/IV cardiovascular disability according to the New York Heart Association Classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll.
• •10. Participants with clinically significant arrhythmia or arrhythmias not stable on medical management.
• •11. Active auto-immune disease requiring systemic immunosuppressive therapy, including uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
• •12. Suspected or confirmed progressive multifocal leukoencephalopathy (PML).
• •13. Requires major surgical procedure within 28 days prior to first dose of study drug. If a subject has major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
• •14. Participants with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
• •15. Known history of drug-specific hypersensitivity or anaphylaxis to either study agent.
• •16. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
• •17. Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
• •18. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• •19. History of other malignancies, except for the following: malignancy surgically resected (or treated with other modalities) with curative intent, adequately treated in situ carcinoma of the breast or cervix uteri, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; early stage prostate cancer on expectant management; malignancy treated with curative intent with no known active disease present for ≥ 3 years.
• •20. Lactating women.
• •21. Active chronic graft-versus-host disease (GVHD) post-allogeneic HCT.
• •22. Uncontrolled active infection:
• •* HIV positive or have active hepatitis B or C infection based on testing performed within 4 weeks of enrollment.
• •* Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded.
• •* Subjects who are hepatitis B core antibody positive (or have a known history of HBV infection) should be monitored quarterly with a quantitative PCR test for HBV DNA. HBV monitoring should last until 12 months after last dose of study drug. Any subject with a rising viral load (above lower limit of detection) should discontinue study drug and have antiviral therapy instituted and a consultation with a physician with expertise in managing hepatitis B. Subjects who are core Ab positive at study enrollment are strongly recommended to start Entecavir before start and until completion of study treatment.
• •* Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded.
• •* Subjects who are positive cytomegalovirus \[CMV\] DNA polymerase chain reaction \[PCR\]).
• •* Subject with any active significant bacterial, fungal or viral (other than those listed) infections.
• •23. Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
• •Noncompliance
• •24. Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
• •* Eligibility should be confirmed per institutional policies.