A Phase 2 Study to Evaluate CD19-Specific Chimeric Antigen Receptor (CAR)-T Cells Combined With Acalabrutinib for Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL)
This phase II trial investigates the side effects of CD19 chimeric antigen receptor (CAR) T cells and acalabrutinib, and to see how well they work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill cancer cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize CD19, a protein on the surface of the cancer cells. These CD19-specific T cells may help the body's immune system identify and kill CD19 positive cancer cells. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CD19 CAR T cells together with acalabrutinib may kill more cancer cells.
• All participants must have the ability to understand and the willingness to sign a written informed consent.
• Participants must agree to allow the use of archival tissue from diagnostic tumor biopsies.
‣ If unavailable, exceptions may be granted with Study PI approval. Note: For research participants who do not speak English, a short form consent may be used with a COH certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed.
• Age Criteria
• Age 18 years and older. Performance Status
• ECOG Performance status ≤ 2 or KPS ≥ 70% (Appendix A) Nature of Illness and Treatment-Related Criteria
• Documented CD19+ MCL by flow cytometry or IHC (from biopsy) if prior CD19 directed therapy was previously used
• a. BM is optional at enrollment IF patient already has biopsy proven disease.
• Participants must be currently receiving acalabrutinib and have been taking acalabrutinib for between 3 and 7 months prior to initiating screening procedures on the study and:
∙ must have at least 1 prior regimen (not including single-agent corticosteroids)
‣ best response to acalabrutinib therapy is MRD+ CR, PR or SD at the time of screening b (1) must have measurable disease by CT scan (≥ 1.5 cm) or evidence of blood, spleen, skin, gastrointestinal (GI) or bone marrow involvement Note: Participants who are on other BTK inhibitors, but will thereafter be switched to acalabrutinib prior to lymphodepletion, may be eligible provided that the duration of all BTK inhibitor therapy was ≤ 3-7 months
• No contraindications to leukapheresis, steroids or tocilizumab Clinical Laboratory Criteria (To be performed within 28 days prior to enrollment)
• Total serum bilirubin ≤ 2.0 mg/dL Participants with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.
• Blood counts:
‣ Absolute Neutrophil count (ANC ≥1000 cells/ul)\*
• Growth factor use within 7 days prior screening is not allowed
⁃ Platelet count ≥75,000/ul. Transfusion with 7 days prior to screening is not allowed\* \*Exception: participants with bone marrow involvement do not need to meet this criteria
⁃ AST \< 3 x ULN
⁃ ALT \< 3 x ULN
⁃ Creatinine clearance of ≥ 50 mL/min per the Cockcroft-Gault formula
⁃ International Normalized Ratio (INR) OR Prothrombin (PT) ≤ 1.5 x ULN
⁃ Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN
⁃ Female of childbearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
⁃ Cardiac function (12 lead-ECG): QTc must be ≤ 480 msec
⁃ Left ventricular ejection fraction \>40%
⁃ Oxygen saturation 92% or above at room air or DLCO of 40% of best predicted Contraception
⁃ Participants of reproductive potential must agree to use highly effective birth control methods throughout therapy and for 2 months after final CAR T cell infusion and/or 2 days after final acalabrutinib dose, whichever is later (See Section 5.12 and Appendix B).