Safety and Efficacy of the Addition of Nemtabrutinib to Lisocabtagene Maraleucel in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia
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
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• The ability to swallow and retain oral medication
‣ NOTE: Administration of nemtabrutinib is not permitted through a percutaneous endoscopic gastro-jejunal (J PEG) tube
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
‣ Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests should include HBsAg and anti-HBV. Hepatitis B screening tests are not required unless:
• Known history of HBV infection,
∙ As mandated by local health authority
• Absolute neutrophil count (ANC) ≥ 500/µL
‣ Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
⁃ No lower limit if cytopenia is related to bone marrow involvement
• Hemoglobin ≥ 8 g/dL
‣ Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
⁃ No lower limit if cytopenia is related to bone marrow involvement
• Platelets ≥ 25 000/µL
‣ Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
⁃ No lower limit if cytopenia is related to bone marrow involvement
• Creatinine ≤ 1.5 × upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl) ≥ 30 mL/min for participant with creatinine levels \> 1.5 × institutional ULN
‣ Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 × ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases)
• International normalized ratio (INR) OR prothrombin time (PT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Cardiac (echocardiogram \[Echo\] or multi-gated acquisition scan \[MUGA\]) ejection fraction ≥ 40%