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
Single group
Nemtabrutinib
DrugGiven PO
Lisocabtagene Maraleucel
Biological/VaccineGiven IV
Complete response (CR)
Will be defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. Binary proportions will be estimated along with 95% confidence intervals. Confidence intervals for binary proportions will be estimated using the Wilson Score method.
Overall response rate
Will be defined by the iwCLL criteria. Binary proportions will be estimated along with 95% confidence intervals. Confidence intervals for binary proportions will be estimated using the Wilson Score method.
Overall survival (OS)
The distribution of OS will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.
Progression free survival (PFS)
Will be defined by the iwCLL criteria. The distribution of PFS will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.
Time to response (TTR)
Will be defined by the iwCLL criteria among responders. The distribution of TTR will be estimated using the method of Kaplan-Meier. Confidence intervals around median time will be estimated using the Brookmeyer Crowley method.
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Fred Hutchinson Cancer Center
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
