RECRUITING

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

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Conditions

Hairy Cell LeukemiaMEK162MEK1InhibitorMEK2

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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....

Official Title

Phase 2 Trial of Encorafenib Plus Binimetinib for Patients With BRAF V600 Mutated Relapsed/Refractory HCL

Quick Facts

Study Start:2020-10-28
Study Completion:2028-07-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04324112

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Histologically confirmed diagnosis of HCL according to morphological and immunophenotypic criteria of WHO classification \[WHO, 2008 revised 2016\] of lymphoid neoplasm. Participants should have at least one of the following indications for therapy:
  2. * Absolute neutrophil count (ANC) \<1 x10(3)/mcL
  3. * Hemoglobin \<10g/dL
  4. * Platelets\<100 x10(3)/mcL
  5. * Symptomatic splenomegaly
  6. * Enlarging HCL mass \> 2cm in short axis
  7. * Leukemia cell count\>5x10(3)/mcL
  8. * 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.
  9. * 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
  10. * Refractory or relapsed disease- defined as either:
  11. * Refractory- no response or disease progression in \<=1 year following first-line treatment with a purine analog, or
  12. * Relapsed- having relapsed following treatment with at least 1 prior purine-analog treatment
  13. * Age \>=18 years
  14. * ECOG performance status \<=2 (Karnofsky \>=60%)
  15. * Participants must have adequate organ and marrow function as defined below:
  16. * Total bilirubin \<= 3x upper limit of normal (ULN), unless consistent with Gilbert s (ratio between total and direct bilirubin \> 5)
  17. * AST and ALT \<= 3x ULN
  18. * Alkaline phosphatase \< 2.5x ULN
  19. * 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 eGFR
  20. * Serum albumin \>= 2 g/dL
  21. * Prothrombin time (PT)/International Normalized Ratio \< 2.5x ULN (If on warfarin, PT/INR \< 3.5x ULN; If on any other anticoagulation, Prothrombin time (PT) \< 2.5x ULN
  22. * Fibrinogen \>= 0.5x lower limit of normal
  23. * The effects of the study drugs on the developing human fetus are unknown therefore participants must use effective methods of contraception as directed below.
  24. * Females of childbearing potential (FOCBP) who are sexually active with a nonsterilized 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 nonhormonal contraception is required for females of childbearing potential during study
  25. * Ability of subject to understand and the willingness to sign a written informed consent document.
  26. * 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
  1. * Participants who have had chemotherapy, immunotherapy, investigational agent or radiotherapy within 4 weeks prior to the start of study treatment.
  2. * Prior therapy with encorafenib and/or binimetinib
  3. * Participants who are receiving any other investigational agents or have received an investigational agent within 14 days prior to the start of study treatment.
  4. * Participants who have undergone major surgery less than or equal to 6 weeks prior to start of study treatment or who have not recovered from side effects of such procedure
  5. * Known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients
  6. * Inability to swallow and retain study drugs.
  7. * 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.
  8. * 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 participants must be on Tenofovir or Entecavir and Hepatitis B Viral deoxyribonucleic acid (DNA) load must be \<2000 IU/mL
  9. * Active second malignancy requiring treatment other than minor resection of indolent cancers like basal cell and squamous skin cancers.
  10. * 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.
  11. * History of an allogeneic bone marrow or stem cell transplant.
  12. * Known history of acute or chronic pancreatitis.
  13. * Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following:
  14. * 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
  15. * Congestive heart failure requiring treatment (New York Heart Association Grade greater than or equal to 2);
  16. * Left ventricular ejection fraction (LVEF) \< 50% as determined by Multigated Acquisition Scan (MUGA) or Transthoracic echocardiogram (TTE);
  17. * 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;
  18. * History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
  19. * Triplicate average baseline QTcF interval greater than or equal to 480 ms.
  20. * 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
  21. * Concurrent neuromuscular disorder that is associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  22. * History or current evidence of 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
  23. * 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.
  24. * 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.
  25. * Note: Participants with thromboembolic events related to indwelling catheters or other procedures may be enrolled
  26. * Participants taking strong CYP3A4 inhibitors and strong/moderate CYP3A4 inducers

Contacts and Locations

Study Contact

Holly Eager (DiFebo), R.N.
CONTACT
(240) 858-7229
holly.eager@nih.gov
Robert J Kreitman, M.D.
CONTACT
(301) 648-7375
kreitmar@mail.nih.gov

Principal Investigator

Robert J Kreitman, M.D.
PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Robert J Kreitman, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-10-28
Study Completion Date2028-07-31

Study Record Updates

Study Start Date2020-10-28
Study Completion Date2028-07-31

Terms related to this study

Keywords Provided by Researchers

  • MEK162
  • MEK1
  • Inhibitor
  • MEK2

Additional Relevant MeSH Terms

  • Hairy Cell Leukemia