Encorafenib Plus Binimetinib for BRAF V600 Mutated Relapsed/Refractory HCL
This study is testing a combination of two drugs, encorafenib and binimetinib, for people with Hairy Cell Leukemia (HCL) that has a specific genetic change called a BRAF V600 mutation. This type of HCL often doesn't respond well to standard chemotherapy. The goal is to see if this drug combination is more effective than a previous treatment (vemurafenib) for HCL with this mutation. You may be able to join if you are 18 or older, have HCL with a BRAF V600 mutation, and your HCL has come back or didn't respond to previous treatment. The study will measure how many people achieve a complete remission (CR) each year. The current status of this study is unclear.
- Study design
- This is an interventional study planning to enroll 28 participants. It is testing two drugs, binimetinib and encorafenib, given continuously.
- What's involved
- You will undergo a medical history, physical exam, and a bone marrow biopsy for screening. Binimetinib and encorafenib will be taken orally every day in 28-day cycles with no breaks.
- Compensation
- Not stated in the trial record.
- Follow-up
- Complete remission rates will be measured every year.
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NCT04324112
Encorafenib Plus Binimetinib for People With BRAF V600 Mutated Relapsed/Refractory HCL
Active, Not Recruiting
PHASE2Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~28 participants
Updated 2026-06-12 on ClinicalTrials.gov
What's tested:binimetinibEncorafenib
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
CR rate
Measured over every year
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Robert J Kreitman, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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 must have BRAF V600 mutation as confirmed from fresh bone marrow aspirate, peripheral blood sample, or lymph node/mass by the Laboratory of Pathology, NCI. This may be done by PCR or sequence-based assays.
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
Refractory or relapsed disease- defined as either:
Refractory- no response or disease progression in \<=1 year following first-line treatment with a purine analog, or
Relapsed- having relapsed following treatment with at least 1 prior purine-analog treatment
Age \>=18 years
Eastern Cooperative Oncology Group (ECOG) performance status \<=2 (Karnofsky \>=60%)
Participants must have adequate organ and marrow function as defined below:
Total bilirubin \<= 3x upper limit of normal (ULN), unless consistent with Gilbert s (ratio between total and direct bilirubin \> 5)
AST and ALT \<= 3x ULN
Alkaline phosphatase \< 2.5x ULN
Serum creatinine \<= 1.5 mg/dL or creatinine clearance \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal calculated using estimated glomerular filtration rate (eGFR)
Serum albumin \>= 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, (PT) \< 2.5x ULN
Fibrinogen \>= 0.5x lower limit of normal
Females of childbearing potential (FOCBP) who are sexually active with a non-sterilized 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 study drug. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. There is a potential for encorafenib to induce CYP3A4, which may reduce the effectiveness of hormonal contraception methods. Therefore, the use of at least 1 form of non-hormonal contraception is required for females of childbearing potential during study
Male participants must use a condom during treatment and through 90 days after the end of systemic exposure to study drug/treatment. If the male participant has a partner that is of child-bearing potential, the partner should also use contraception through
Nursing participants must be willing to discontinue nursing from study treatment initiation through 14 days after the last dose of the study drugs.
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
Exclusion
Participants who have had chemotherapy, immunotherapy, investigational agent or radiotherapy within 4 weeks prior to the start of study treatment.
Prior therapy with encorafenib and/or binimetinib
Participants who are receiving any other investigational agents or have received an investigational agent within 14 days prior to the start of study treatment.
Participants who have undergone major surgery \<=6 weeks prior to start of study treatment or who have not recovered from side effects of such procedure
Known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients
Inability to swallow and retain study drugs.
Pregnant women as evaluated by a positive serum or urine beta-human chorionic gonadotropin (beta-hCG).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac dysfunction, uncontrolled pulmonary infection, pulmonary edema or psychiatric illness/social situations that would limit compliance with study requirements.
Evidence of active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. Note: Participants with laboratory evidence of cleared HBV or HCV infection may be enrolled. If positive for Hepatitis B core antibody or surface antigen the participant must be on Tenofovir or Entecavir and Hepatitis B deoxyribonucleic acid (DNA) viral load must be \<2000 IU/mL
Active second malignancy requiring treatment other than minor resection of indolent cancers like basal cell and squamous skin cancers.
Human immunodeficiency virus (HIV)-positive participants unless taking appropriate anti-HIV medications with a CD4 count of \> 200. Otherwise, there may be an increased risk of infections.
History of an allogeneic bone marrow or stem cell transplant.
Known history of chronic pancreatitis.
Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following:
History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) \<3months prior to initiation of study therapy
Congestive heart failure requiring treatment (New York Heart Association Grade greater than or equal to 2);
Left ventricular ejection fraction (LVEF) \< 50% as determined by Multigated Acquisition Scan (MUGA) or Transthoracic echocardiogram (TTE);
Uncontrolled hypertension defined as persistent systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 100 mmHg despite current therapy;
History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
Triplicate average baseline QTcF interval greater than or equal to 480 ms.
Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal
Concurrent neuromuscular disorder that is associated with elevated creatinine kinase CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of maculopathy or retinopathy for which there is an increased risk
History of thromboembolic or cerebrovascular events less than or equal to 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli.
Note: Participants with either deep vein thrombosis or pulmonary emboli that does not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of anticoagulants for at least 4 weeks.
Note: Participants with thromboembolic events related to indwelling catheters or other procedures may be enrolled
Participants taking strong CYP3A4 inhibitors and strong/moderate CYP3A4 inducers
What this trial measures
- CR rateevery year
determine if treatment with combination encorafenib and binimetinib in BRAF V600 mutant + HCL is associated with a CR rate which exceeds that of vemurafenib