This phase Ib/II trial studies the side effects and efficacy of maintenance acalabrutinib following cellular therapy in treating patients with large B-cell lymphoma at very high risk of the cancer coming back. Acalabrutinib is a small molecular inhibitor that may interfere with the ability of cancer cells to grow and spread.
Ages 18-70 years
High grade B-cell lymphoma (double or triple hit) with rearrangements in bcl-2 and/or bcl-6, and rearrangement in myc
Large B-cell lymphoma with a history of secondary CNS involvement
Histologic transformation of indolent lymphoma to large B-cell lymphoma, including marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), lymphoplasmacytic leukemia, or Waldenstrom macroglobulinemia
Cord blood as donor source in alloHCT
New York Heart Association Class III or IV
Left ventricular ejection fraction < 50%
Estimated glomerular filtration rate < 30 mL/min
Parallel
Acalabrutinib
DrugGiven PO
Permanent discontinuation of acalabrutinib
Tolerability will be determined by the number of patients who permanently discontinue acalabrutinib within 12 months from cellular therapy due to intolerance. The proportion of patients with acalabrutinib discontinuation will be reported along with 95% and 90% confidence intervals.
Progression-free survival (PFS)
The 1-year PFS will be evaluated based on progression of disease per Lugano criteria or death, and will be reported based on Kaplan-Meier estimates along with 95% confidence interval.
PFS
Will be reported based on 95% confidence intervals at annual time points.
Overall survival
Time from cellular therapy to death due to any cause, assessed at 1 and 5 years based on Kaplan-Meier estimates along with 95% confidence interval
Rate of conversion from partial response following chimeric antigen receptor (CAR) T-cell therapy to complete response after the addition of acalabrutinib maintenance
Will be reported based on 95% confidence intervals.
CAR T-cell persistence
CAR T-cell persistence measured by mass cytometry upon enrollment, 90 days after initiation of acalabrutinib, and at time of relapse.
Immunophenotyping of peripheral blood mononuclear cells
Types and numbers of proteins present on the leukemia cell surface via mass cytometry upon enrollment, 90 days after initiation of acalabrutinib, and at time of relapse
Intracellular cytokine and phospho-protein profiling of peripheral blood mononuclear cells
Types of proteins involved in cell signaling in leukemia cells via mass cytometry upon enrollment, 90 days after initiation of acalabrutinib, and at time of relapse.
Acalabrutinib metabolite
Acalabrutinib metabolite detected in the cerebral spinal fluid at 1-3 weeks after initiation of acalabrutinib in participants with history of secondary central nervous system lymphoma.
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Jonsson Comprehensive Cancer Center
Lead sponsor
AstraZeneca
Collaborator
