Phase 2 Trial for Binimetinib for Patients With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant
National Cancer Institute (NCI)
Summary
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....
Description
Background: * Hairy cell leukemia (HCL) is an indolent B-cell leukemia comprising 2 percent of all leukemias, or approximately 1300 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. The median survival is only \~6 years compared to \>25 years for classic HCL. * CD25+ classic-appearing HCL-cells that express unmutated IGHV4-34+ immunoglobulin rearrangement, are wild-type for…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * 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 ha…
Interventions
- Drugbinimetinib
Binimetinib will be given orally at a dose of 45mg BID continuously for 28-day cycles with no resting period between cycles.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland