Phase 2 Trial for Binimetinib for Patients With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant
Background: Most people with hairy cell leukemia have a BRAF gene mutation. They can be treated with BRAF inhibitors, drugs that target this mutation. For people who do not have this mutation, BRAF inhibitors are not a treatment option. We found that in hairy cell leukemia, when BRAF is not mutated, the MEK gene frequently is. Binimetinib is a MEK inhibitor which targets MEK. It is important to determine if this drug can be a good treatment option in those who cannot benefit treatment with BRAF inhibitors.
Objective: To see if binimetinib is an effective treatment for hairy cell leukemia that does not have a BRAF mutation.
Eligibility: People ages 18 and older with hairy cell leukemia without a mutation in the BRAF gene and whose disease either did not respond to treatment or came back after treatment
Design: Participants will be screened with: * Medical history * Physical exam * Blood and urine tests * Lung and heart tests * Eye exam * Bone marrow biopsy: A needle will be injected through the participant s skin into the bone to remove a sample of marrow. * CT or MRI scan: Participants will lie in a machine that takes pictures of the body. They might receive a contrast agent by vein. Before they start treatment, participants will have an abdominal ultrasound, pulmonary function tests, and exercise stress tests. Participants will take binimetinib by mouth twice daily in 28-day cycles. They will keep a medication diary. Participants will have at least one visit before every cycle. Visits will include repeats of some screening tests. Participants may continue treatment as long as their disease does not get worse and they do not have bad side effects. About a month after their last dose of treatment, participants will have a follow-up visit. They will then have visits once a year....
• Histologically confirmed diagnosis of HCL or HCLv according to morphological and immunophenotypic criteria of World Health Organization (WHO) classification \[WHO, 2008 revised 2016\] of lymphoid neoplasm. Participants should have at least one of the following indications for therapy:
‣ Absolute neutrophil count (ANC) \<1 x10\^3/mcL
⁃ Hemoglobin \<10g/dL
⁃ Platelets\<100 x10\^3/mcL
⁃ Symptomatic splenomegaly
⁃ Enlarging HCL mass or bone lesion \> 2cm in short axis
⁃ Leukemia cell count \>5x10\^3/mcL
⁃ Leukemic doubling time \<6 months
∙ Participants who have eligible blood counts within 4 weeks prior to initiation of study therapy will not be considered ineligible if subsequent blood counts prior to initiation of study therapy fluctuate and become ineligible up until the time of the initiation of study therapy.
• Refractory or relapsed disease - defined as either:
‣ Refractory- no response or disease progression in less than or equal to 1 year following first-line treatment with a purine analog, or
⁃ Relapsed- having relapsed following treatment with at least 1 prior purine-analog treatments
• Participants must be BRAF WT as confirmed from fresh bone marrow aspirate and/or peripheral blood sample, or lymph node/mass by the Laboratory of Pathology, NCI
• Participants who are ineligible for, unable to obtain in a timely manner, cannot access, unwilling to undergo or have failed Moxetumomab Pasudotox trial at NCI
• Age greater than or equal to 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent).
• Adequate organ and marrow function as defined below:
‣ Total bilirubin less than or equal to 3x upper limit of normal (ULN), unless consistent with Gilbert s (ratio between total and direct bilirubin \> 5)
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3x ULN
⁃ Alkaline phosphatase \<= 5x ULN
⁃ Serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal calculated using estimated glomerular filtration rate (eGFR)
⁃ Serum albumin greater than or equal to 2 g/dL
⁃ Prothrombin time (PT)/International Normalized Ratio (INR) \< 2.5x ULN (If on warfarin, PT/INR \< 3.5x ULN; If on any other anticoagulation, Prothrombin time (PT) \< 2.5x ULN
⁃ Fibrinogen greater than or equal to 0.5x lower limit of normal
• The effects of binimetinib on the developing human fetus are unknown therefore participants must use effective methods of contraception as directed below.
• Females of childbearing potential (FOCBP) who are sexually active with a nonsterilized male partner must use a highly effective method of contraception and not donate ova prior to study entry and or the duration of study treatment and until 30 days after the last dose of binimetinib. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are premenarchal or postmenopausal (defined as 12 months with no menses without an alternative medical cause). A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Not all methods of contraception are highly effective. Female subjects must use a hormonal method in addition to a barrier method alone, to minimize the chance of pregnancy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Non-sterilized male participants who are sexually active with a female partner of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, and not donate sperm from study entry until 90 days after the last dose of binimetinib.
• Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 days after the last dose of the study drug.
• Ability of participant to understand and the willingness to sign a written informed consent document.
• Must co-enroll in study 10-C-0066: Collection of Human Samples to Study Hairy Cell and other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment