This phase II trial studies how well the addition of nemtabrutinib to lisocabtagene maraleucel in treating patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Nemtabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lisocabtagene maraleucel is a type of treatment called chimeric antigen receptor (CAR) T-cell therapy, in which a patient's T-cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T-cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T-cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T-cells are grown in the laboratory and given to the patient by infusion for treatment. Adding nemtabrutinib to lisocabtagene maraleucel may be an effective treatment for relapsed/refractory CLL/SLL.
Confirmed diagnosis of CLL/SLL per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) classification
Measurable disease by imaging (lymph node [LN] > 1.5cm) or absolute lymphocyte count (ALC) (> 5000/μL) or marrow involvement of at least 30% by flow cytometry
Eligible for lisocabtagene maraleucel (liso-cel) as standard-of-care per Food and Drug Administration (FDA) label for CLL/SLL
At least 18 years of age at time of study enrollment
Diagnosis of Richter Transformation
Clinically significant (symptomatic) central nervous system (CNS) involvement at time of study enrollment. Previously treated CNS disease is allowed if the participant is asymptomatic. Incidental findings including positive cerebral spinal fluid (CSF) studies are not exclusionary
Active infection and uncontrolled infection
Active HBV/hepatitis C virus (HCV) infection
Fred Hutchinson Cancer Center
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator