Hairy Cell LeukemiaPhase 2NCT04324112
Encorafenib Plus Binimetinib for People With BRAF V600 Mutated Relapsed/Refractory HCL
A Phase 2 study testing binimetinib and Encorafenib in people with Hairy Cell Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hairy Cell Leukemia
- What is being tested?
- binimetinib and Encorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2020to 30 Jun 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- Leukemia cell count>5x10(3)/mcL
- 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.
- 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
- treatment in this study. 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. 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.
- --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
- 90 days after the end of systemic exposure to study drug/treatment. In addition, male participants must refrain from donating sperm during the study treatment and through 90 days after the end of systemic exposure to study drug/treatment. Males who have had a vasectomy qualify as having met the requirement for a highly effective birth control method.
- 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
Who cannot join
- 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.
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- 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
- absorption), or recent (less than or equal to 3 months) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs.
- 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
- of MEK induced exudation (e.g., Central Serous Retinopathy).
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase 2 Trial of Encorafenib Plus Binimetinib for Patients With BRAF V600 Mutated Relapsed/Refractory HCL
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.
Read more
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....
Read the detailed 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 pathway, causing increased phosphorylation (hyper-activation) of MEK, followed by ERK, therefore promoting the proliferation and survival of HCL cells.
- The BRAF inhibitor, vemurafenib, when used as a single agent for the treatment of HCL achieved high response rate with CR rate of 38% in 50 patients reported from 2 trials, however, treatment was limited to several months and responses lacked durability, with median CR duration of 19 months in 1 trial. In this trial, 100% of the CRs were positive for minimal residual disease (MRD) by immunohistochemistry (IHC), and failure to eradicate MRD after several months of vemurafenib likely lead to the lack of CR durability.
- In a recent trial of combined inhibition of BRAF and MEK using dabrafenib and trametinib treatment, 49% of 41 evaluable patients achieved CR, and MRD was eradicated in 15% of patients on this trial. At NIH, we enrolled a total of 28 HCL patients on this trial and achieved a CR rate of 68% amongst our patients by managing toxicity and allowing patients to remain on treatment.
- A major challenge in the long-term treatment of HCL patients with dabrafenib and trametinib is managing fever, which has necessitated long-term or intermittent steroids use for most patients.
- In the COLOMBUS trial, the combination of the BRAF inhibitor, encorafenib and the MEK inhibitor, binimetinib was found to be superior to vemurafenib for BRAF V600E+ melanoma with respect to PFS and OS and was well tolerated with low rates of toxicities including pyrexia.
- To our knowledge, neither encorafenib nor binimetinib has been tested in HCL, but the low rate of pyrexia with encorafenib plus binimetinib in melanoma suggests that this combination may be well tolerated in HCL.
Objective:
- To determine if treatment with combination encorafenib and binimetinib in BRAF V600 mutant + HCL is associated with a CR rate which exceeds that of vemurafenib.
Eligibility:
- BRAF V600 mutant HCL with at least 1 prior purine analog treatment
- Need for treatment, as evidenced by any one of the following: ANC <1 x10^3/mcL, Hgb <10g/dL, Platelet count <100 x10^3/mcL, leukemia cell count >5 x10^3/mcL, symptomatic splenomegaly, enlarging HCL mass > 2cm (>0.5cm if in central nervous system [CNS]) in short axis
- Greater than or equal to 18 years of age
- No uncontrolled infection, cardiopulmonary dysfunction, or secondary malignancy requiring treatment.
- No chemotherapy, immunotherapy, investigational agent or radiotherapy within 4 weeks prior to the start of study treatment.
Design:
- Phase 2 trial, single arm, non-randomized trial to determine if the combination of encorafenib and binimetinib achieves a CR rate in HCL which is historically higher than that of vemurafenib.
- Simon optimal 2-phase design will be used to rule out an unacceptable CR rate of 35% in favor of an improved 55% CR rate.
- Initially 12 evaluable participants will be enrolled. If 5 or more achieve CR, then accrual will continue to a total of 32 evaluable participants
- Encorafenib will be given at a dose of 450mg QD and binimetinib at a dose of 45mg BID for as long as participants can continue dosing chronically without significant toxicity or a trial off therapy due to achievement of MRD negative complete remission or PR/CR in which they would like a trial off therapy. Participants may return to therapy within 2 years of stopping treatment if evidence of disease returns.
- Conditions
- Hairy Cell Leukemia
- Being tested
- binimetinib, Encorafenib
- Keywords
- MEK162, MEK1, Inhibitor, MEK2
- Medical subject headings
- Leukemia, Hairy Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
binimetinibDrug
Binimetinib will be given orally at a dose of 45mg BID continuously for 28-day cycles with no resting period between cycles.
EncorafenibDrug
Encorafenib will be given orally at a dose of 450mg QD continuously for 28-day cycles with no resting period between cycles.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1/Experimental therapy | Experimental | Treatment with encorafenib and binimetinib Receives: Drug: binimetinib; Drug: Encorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
CR rate
determine if treatment with combination encorafenib and binimetinib in BRAF V600 mutant + HCL is associated with a CR rate which exceeds that of vemurafenib
Measured: every year
Secondary outcomes (7)
MRD negative CR
Fraction of patients who achieve MRD negative CR after treatment with encorafenib and binimetinib
Measured: every year
time to next treatment
duration of time from the start of the study drugs to next line of treatment
Measured: every year
overall survival
the time from the start of the treatment until time of death from any cause
Measured: every year
event free survival
the time from study enrollment to the first occurrence of progression, relapse after response, or death from any cause
Measured: every year
duration of response
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
Measured: every year
progression free-survival
duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first
Measured: every year
rate of pyrexia
fraction of patients that have pyrexia at any time while on study
Measured: every year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start28 Oct 2020
- Primary completion20 May 2026
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hairy Cell LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert J Kreitman, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04324112
- Sponsor's protocol ID
- 200076
- Other IDs
- 20-C-0076
- Status last verified
- 10 Jun 2026
- First submitted
- 26 Mar 2020
- Last updated
- 12 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request.
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Encorafenib Plus Binimetinib for Patients With BRAF V600 Mutated Relapsed/Refractory HCL
- ClinicalTrials.gov ID
- NCT04324112
- Acronym / sponsor ID
- 200076
- Conditions
- Hairy Cell Leukemia
- Keywords
- MEK162, MEK1, Inhibitor, MEK2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 20 May 2026 (actual)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 27 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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....
Detailed 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 pathway, causing increased phosphorylation (hyper-activation) of MEK, followed by ERK, therefore promoting the proliferation and survival of HCL cells.
- The BRAF inhibitor, vemurafenib, when used as a single agent for the treatment of HCL achieved high response rate with CR rate of 38% in 50 patients reported from 2 trials, however, treatment was limited to several months and responses lacked durability, with median CR duration of 19 months in 1 trial. In this trial, 100% of the CRs were positive for minimal residual disease (MRD) by immunohistochemistry (IHC), and failure to eradicate MRD after several months of vemurafenib likely lead to the lack of CR durability.
- In a recent trial of combined inhibition of BRAF and MEK using dabrafenib and trametinib treatment, 49% of 41 evaluable patients achieved CR, and MRD was eradicated in 15% of patients on this trial. At NIH, we enrolled a total of 28 HCL patients on this trial and achieved a CR rate of 68% amongst our patients by managing toxicity and allowing patients to remain on treatment.
- A major challenge in the long-term treatment of HCL patients with dabrafenib and trametinib is managing fever, which has necessitated long-term or intermittent steroids use for most patients.
- In the COLOMBUS trial, the combination of the BRAF inhibitor, encorafenib and the MEK inhibitor, binimetinib was found to be superior to vemurafenib for BRAF V600E+ melanoma with respect to PFS and OS and was well tolerated with low rates of toxicities including pyrexia.
- To our knowledge, neither encorafenib nor binimetinib has been tested in HCL, but the low rate of pyrexia with encorafenib plus binimetinib in melanoma suggests that this combination may be well tolerated in HCL.
Objective:
- To determine if treatment with combination encorafenib and binimetinib in BRAF V600 mutant + HCL is associated with a CR rate which exceeds that of vemurafenib.
Eligibility:
- BRAF V600 mutant HCL with at least 1 prior purine analog treatment
- Need for treatment, as evidenced by any one of the following: ANC <1 x10^3/mcL, Hgb <10g/dL, Platelet count <100 x10^3/mcL, leukemia cell count >5 x10^3/mcL, symptomatic splenomegaly, enlarging HCL mass > 2cm (>0.5cm if in central nervous system [CNS]) in short axis
- Greater than or equal to 18 years of age
- No uncontrolled infection, cardiopulmonary dysfunction, or secondary malignancy requiring treatment.
- No chemotherapy, immunotherapy, investigational agent or radiotherapy within 4 weeks prior to the start of study treatment.
Design:
- Phase 2 trial, single arm, non-randomized trial to determine if the combination of encorafenib and binimetinib achieves a CR rate in HCL which is historically higher than that of vemurafenib.
- Simon optimal 2-phase design will be used to rule out an unacceptable CR rate of 35% in favor of an improved 55% CR rate.
- Initially 12 evaluable participants will be enrolled. If 5 or more achieve CR, then accrual will continue to a total of 32 evaluable participants
- Encorafenib will be given at a dose of 450mg QD and binimetinib at a dose of 45mg BID for as long as participants can continue dosing chronically without significant toxicity or a trial off therapy due to achievement of MRD negative complete remission or PR/CR in which they would like a trial off therapy. Participants may return to therapy within 2 years of stopping treatment if evidence of disease returns.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1/Experimental therapy | Experimental | Drug: binimetinib, Drug: EncorafenibTreatment with encorafenib and binimetinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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:
- 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.
- 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:
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| binimetinibBinimetinib will be given orally at a dose of 45mg BID continuously for 28-day cycles with no resting period between cycles. | Drug | Arm 1/Experimental therapy |
| EncorafenibEncorafenib will be given orally at a dose of 450mg QD continuously for 28-day cycles with no resting period between cycles. | Drug | Arm 1/Experimental therapy |
Primary outcome
CR rate
Time frame: every 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
7 secondary outcomes
MRD negative CR
Time frame: every year
time to next treatment
Time frame: every year
overall survival
Time frame: every year
event free survival
Time frame: every year
duration of response
Time frame: every year
progression free-survival
Time frame: every year
rate of pyrexia
Time frame: every year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert J Kreitman, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing binimetinib and Encorafenib in people with Hairy Cell Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CR rate (time frame: every year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026; AzTrials last refreshed its copy on 7 Nov 2026.