Phase 2 Trial of Encorafenib Plus Binimetinib for Patients With BRAF V600 Mutated Relapsed/Refractory HCL
National Cancer Institute (NCI)
Summary
Background: Hairy cell leukemia (HCL) does not usually respond to chemotherapy. Most people with HCL have a BRAF gene mutation. This can increase the growth of cancer cells. Vemurafenib has been tested to treat these people. However, researchers think a combination of drugs might work better. Objective: To test if treatment with a combination of encorafenib and binimetinib in BRAF mutant HCL is more effective than treatment with vemurafenib. Eligibility: People ages 18 and older with BRAF mutant HCL that did not respond to or came back after treatment Design: Participants will be screened with: Medical history Physical exam Bone marrow biopsy: A needle will be injected through the participant s skin and into a bone to remove liquid. Blood and urine tests Heart and lung function tests CT or MRI scan: Participants will lie in a machine that takes pictures of the body. They may have a contrast agent injected into a vein. Eye exam Participants will take the study drugs by mouth in 28-day cycles. They will take encorafenib daily. They will take binimetinib twice daily. They will keep a pill diary. Participants will take their temperature daily. Participants will have at least 1 visit before each cycle. Visits will include repeats of some screening tests. They will also include abdominal ultrasounds, exercise stress tests, and skin evaluations. 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. Then they will have annual follow-ups....
Description
Background: * Hairy cell leukemia (HCL) is an indolent B-cell leukemia comprising 2% of all leukemias, or approximately 1300 new cases/year in the US. The nucleoside analogs cladribine and pentostatin are highly active as monotherapy with complete remission (CR) rates of 80 to 90%. However, there is no cure from chemotherapy and patients eventually relapse with worse efficacy and cumulative toxicity (stem cell damage and neuropathy) with each repeated chemotherapy course. * About 90% of classic HCL patients have the BRAF V600E mutation, which leads to Ras-independent activation of the MAPK pa…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Histologically confirmed diagnosis of HCL 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 \> 2cm in short axis (\>0.5cm in short axis for CNS mass) * Leukemia cell count\>5x10(3)/mcL Participants who have eligible blood counts…
Interventions
- Drugbinimetinib
Binimetinib will be given orally at a dose of 45mg BID continuously for 28-day cycles with no resting period between cycles.
- DrugEncorafenib
Encorafenib will be given orally at a dose of 450mg QD continuously for 28-day cycles with no resting period between cycles.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland