Nemtabrutinib and Venetoclax for the Treatment of Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
brief summary
This phase II trial tests how well nemtabrutinib and venetoclax work in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cells (a type of white blood cell) in cancers such as CLL or SLL at abnormal levels. This may help keep cancer cells from growing and spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Giving nemtabrutinib in combination with venetoclax may kill more cancer cells in patients with CLL or SLL.
detailed description
PRIMARY OBJECTIVE:
I. To determine rates of undetectable minimal residual disease (MRD) (threshold 10\^-6) in the peripheral blood using adaptive ClonoSeq next generation sequencing (NGS) following 14 cycles of therapy with nemtabrutinib plus venetoclax in patients with treatment-naïve CLL/SLL.
SECONDARY OBJECTIVES:
I. To determine safety and toxicity profile for patients treated with the combination of nemtabrutinib plus venetoclax for treatment-naïve CLL/SLL.
II. To determine progression free survival (PFS) for patients treated with the combination of nemtabrutinib plus venetoclax for treatment-naïve CLL/SLL.
III. To assess time to next treatment for participants treated with the combination of nemtabrutinib plus venetoclax for treatment-naïve CLL/SLL.
IV. To assess treatment response for participants treated with the combination of nemtabrutinib plus venetoclax for treatment-naïve CLL/SLL.
V. To assess for changes in patient fatigue and health related quality of life (HRQoL) measures during and after treatment with nemtabrutinib and venetoclax as measured by Patient-Reported Outcomes Measurement Information System (PROMIS)® version (v) 1.0 Fatigue Short Form 13a and European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire - Chronic Lymphocytic Leukemia 17 (EORTC QLQ-CLL17) surveys.
EXPLORATORY OBJECTIVES:
I. To determine whether baseline fluorescence in situ hybridization (FISH) or NGS abnormalities affect MRD or PFS with the combination of nemtabrutinib and venetoclax.
II. To determine how the combination of nemtabrutinib and venetoclax alters number and function of T, B, and natural killer (NK) cells in the peripheral blood prior to, during and after therapy.
III. To determine the kinetics of MRD following treatment with nemtabrutinib plus venetoclax.
IV. To determine whether nemtabrutinib primes cells toward apoptosis using BH3 profiling before treatment and prior to initiation of venetoclax.
official title
A Phase 2 Study of Nemtabrutinib and Venetoclax as Frontline Treatment for Chronic Lymphocytic Leukemia (CLL)