Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
National Heart, Lung, and Blood Institute (NHLBI)
Summary
Background: Chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) are diseases in which the body makes too many white blood cells that do not work properly. Because white cells play a role in immune function, people with CLL/SLL may be at greater risk of infections. CLL/SLL can be controlled with drugs, but many people develop resistance, and the treatments stop working. Objective: To test a new drug (nemtabrutinib) in people with CLL/SLL. Eligibility: People aged 18 years or older with CLL/SLL that persists despite treatment. Design: Participants will be screened. They will have imaging scans, blood and urine tests, and a test of their heart function. They will have a bone marrow biopsy: a sample of tissue and fluids will be drawn from inside their hip bone. They may also have a sample cut from a swollen lymph node, if one is safe to access. Nemtabrutinib is a tablet taken by mouth. Participants will take the drug once a day at home in 4-week cycles. They will have clinic visits at least every 4 weeks for the first 6 months and then every 3 months after that. Biopsies, imaging exams, and other tests may be repeated at these visits. Participants may also undergo lymphapheresis: Blood will be drawn from a tube inserted into a vein. The blood will pass through a machine that separates out cancer and immune cells. The remaining blood will be returned to the body through a different tube. Participants may stay in the study as long as the drug is helping them.
Description
Study Description: This is a phase 2 study of nemtabrutinib for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) refractory to treatment with covalent Bruton tyrosine kinase inhibitor (BTKi) or pirtobrutinib, and previously treated with B-cell lymphoma 2 inhibitor (BCL2i). Subjects will be treated with nemtabrutinib 65 mg by mouth once daily until disease progression or toxicity. Efficacy will be evaluated separately in CLL/SLL refractory to covalent BTKi (cBTKi) and in CLL/SLL refractory to pirtobrutinib. Efficacy will also be evaluated in molecular subgroups based on B…
Eligibility
- Age range
- 18–100 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Age \>=18 years. CLL/SLL is extremely rare in patients \< 18 years old. 2. Ability to comprehend the investigational nature of the study and provide informed consent 3. Confirmed diagnosis of CLL or SLL according to International Workshop on CLL (iwCLL) guidelines 1. Coexpression of CD5, CD19, CD20, and CD23 expression and light-chain restriction 2. CLL: clonal B-lymphocytosis \>=5,000 cells/mL OR SLL: lymphadenopathy with the tissue morphology of CLL b…
Interventions
- DrugNemtabrutinib
Nemtabrutinib 65 mg will be given orally once daily in 28-day cycles and continue treatment until disease progression, unacceptable toxicity, or another discontinuation criterion is met.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland