Encorafenib Plus Binimetinib for People With BRAF V600 Mutated Relapsed/Refractory HCL

NCT04324112 | Recruiting Phase 2

• 2 other identifiers: 20007620-C-0076
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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....

Conditions

Hairy Cell Leukemia

Keywords

MEK162; MEK1; Inhibitor; MEK2

Outcome Measures

Primary Outcomes (1)

• 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

  every year

Secondary Outcomes (7)

• MRD negative CR

  every year

• time to next treatment

  every year

• overall survival

  every year

• event free survival

  every year

• duration of response

  every year

Study Arms (1)

Arm 1/Experimental therapy

EXPERIMENTAL

Treatment with encorafenib and binimetinib

Drug: binimetinib; Drug: Encorafenib

Interventions

binimetinib DRUG

Binimetinib will be given orally at a dose of 45mg BID continuously for 28-day cycles with no resting period between cycles.

Arm 1/Experimental therapy

Encorafenib DRUG

Encorafenib will be given orally at a dose of 450mg QD continuously for 28-day cycles with no resting period between cycles.

Arm 1/Experimental therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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%)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Hairy Cell

Interventions

binimetinib; encorafenib

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Robert J Kreitman, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Holly M Eager, R.N.

CONTACT

(240) 858-7229; holly.eager@nih.gov

Robert J Kreitman, M.D.

CONTACT

(301) 648-7375; kreitmar@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2020
• First Posted: March 27, 2020
• Study Start: October 28, 2020
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: March 31, 2026

Record last verified: 2026-03-27

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)