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 18 years and older. Performance Status
Allogeneic hematopoietic cell transplantation (HCT) within the last 6 months.
Autologous HCT within the last 3 months.
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).
Participants known to have mutations associated with resistance to BTK inhibitors from prior studies.
Single group
Acalabrutinib
DrugGiven PO
CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes
Biological/VaccineGiven IV
Occurrence of dose-limiting toxicities (DLTs) (Safety Lead-in)
Rates and associated 95% Clopper and Pearson exact confidence interval (CI) will be estimated for DLTs at the safe dose.
Complete response (CR) (Phase II)
Response will be assessed based on Lugano classification. CR rate is defined as the proportion of response-evaluable participants who achieve a best response of CR within 6 months of CAR T-cell infusion and concurrent acalabrutinib therapy. Rates and associated 95% Clopper and Pearson exact CI will be estimated for CR within 6 months.
Time to CR
Descriptive statistics will be used to summarize the time to CR among those who achieve CR.
Duration of CR
Duration of CR will be assessed using Kaplan Meier methods.
Best response
Defined as the best response documented at any time after CAR T cell infusion through 1 year after CAR T cell infusion or the start of any non-protocol anti-lymphoma therapy, whichever occurs first. Best response will be presented in tabular format including counts and percentages.
Progression-free survival (PFS)
Progression-free survival will be assessed using Kaplan Meier methods.
CD19 CAR T cell persistence
Rates and associated 95% Clopper and Pearson exact CI will be estimated for CD19 CAR T cell persistence at 28 days.
Presence of CD19CAR immunogenicity
Rates and associated 95% Clopper and Pearson exact CI will be estimated for presence of CD19CAR immunogenicity.
Duration of CR from completion of acalabrutinib
This analysis will include only participants who have achieved CR and completed 6 cycles of acalabrutinib, and it will be defined as the time from last dose of acalabrutinib through disease relapse, progression or death, whichever is earlier. Will be assessed using Kaplan Meier methods.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
