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. ...
Name: binimetinib
Description: Percentage of patients with the best overall response of CR or PR to therapy
Measure: overall response rate Time: every yearDescription: the time criteria are met for CR or PR (whichever is recorded first) until the first date that patient no longer qualifies as a PR
Measure: CR rate Time: every yearDescription: duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first
Measure: Progression free survival Time: every yearDescription: the time from the start of the treatment until time of death from any cause
Measure: Overall survival Time: every yearDescription: duration of time from the start of the binimetinib to next line of treatment
Measure: time to next treatment Time: every yearDescription: The fraction of patients with toxicity noted will be reported by grade and type of toxicity identified.
Measure: safety Time: every 4 weeksDescription: determine whether the response to binimetinib is different in patients with and without MAP2K1 (MEK mutations), in patients for which MEK status is known
Measure: different response relative to MAP2K1 mutations Time: every yearAllocation: N/A
Single Group Assignment
There is one SNP
Hairy Cell Leukemia Leukemia Leukemia, Hairy Cell Background: - Hairy cell leukemia (HCL) is an indolent B-cell leukemia comprising 2% of all leukemias, or approximately 1900 new cases per year in the US. - BRAF V600E mutation is very common in classic HCL. - HCL variant (HCLv) is wild type for BRAF and is more aggressive compared to classic HCL due to its lower response and shorter duration of response to standard purine analog chemotherapy. --- V600E ---
- While BRAF and MEK combination inhibition is making an impact in the treatment of BRAF V600E mutated HCL, this treatment is not applicable for patients with BRAF-WT HCL/HCLv. --- V600E ---