Testing the Effectiveness of the Anti-cancer Drug, Mirdametinib, in Treating Relapsed, Refractory Chronic Lymphocytic Leukemia

PRIMARY OBJECTIVE: I. To evaluate the best objective response rate (ORR) with single agent mirdametinib. ORR will be composed of complete response (CR), CR with incomplete marrow recovery (CRi), and partial remission (PR) as defined by the 2018 Modified International Workshop on Chronic Lymphocytic Leukemia (iwCLL) National Cancer Institute-Working Group (NCI-WG) criteria, which includes PR with lymphocytosis (Hallek et al., 2018). SECONDARY OBJECTIVES: I. To determine the effect of mirdametinib on progression-free survival (PFS). II. To evaluate the duration of response (DOR) for mirdametinib in relapsed refractory chronic lymphocytic leukemia (R/R CLL). III. To determine the effect of mirdametinib on overall survival (OS). IV. To evaluate the safety and tolerability of mirdametinib, including the rates of high grade (3+) events, and rates of discontinuations and dose modifications. OUTLINE: Patients receive mirdametinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow biopsy, blood sample collection, echocardiography, and computed tomography (CT) throughout the study. After completion of study treatment, patients are followed up at 30 days then every 2 months until starting a new therapy followed by every 3 months for up to a total of 5 years.