RECRUITING

Binimetinib for People With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant

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Conditions

Hairy Cell LeukemiaMEK1InhibitorMEK2MEK162

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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: Most people with hairy cell leukemia have a BRAF gene mutation. They can be treated with BRAF inhibitors, drugs that target this mutation. For people who do not have this mutation, BRAF inhibitors are not a treatment option. We found that in hairy cell leukemia, when BRAF is not mutated, the MEK gene frequently is. Binimetinib is a MEK inhibitor which targets MEK. It is important to determine if this drug can be a good treatment option in those who cannot benefit treatment with BRAF inhibitors. Objective: To see if binimetinib is an effective treatment for hairy cell leukemia that does not have a BRAF mutation. Eligibility: People ages 18 and older with hairy cell leukemia without a mutation in the BRAF gene and whose disease either did not respond to treatment or came back after treatment Design: Participants will be screened with: * Medical history * Physical exam * Blood and urine tests * Lung and heart tests * Eye exam * Bone marrow biopsy: A needle will be injected through the participant s skin into the bone to remove a sample of marrow. * CT or MRI scan: Participants will lie in a machine that takes pictures of the body. They might receive a contrast agent by vein. Before they start treatment, participants will have an abdominal ultrasound, pulmonary function tests, and exercise stress tests. Participants will take binimetinib by mouth twice daily in 28-day cycles. They will keep a medication diary. Participants will have at least one visit before every cycle. Visits will include repeats of some screening tests. 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. They will then have visits once a year....

Official Title

Phase 2 Trial for Binimetinib for Patients With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant

Quick Facts

Study Start:2021-01-07
Study Completion:2028-07-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04322383

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 or HCLv 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:
  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 or bone lesion \> 2cm in short axis
  7. * Leukemia cell count \>5x10\^3/mcL
  8. * Leukemic doubling time \<6 months
  9. * Refractory or relapsed disease - defined as either:
  10. * Refractory- no response or disease progression in less than or equal to 1 year following first-line treatment with a purine analog, or
  11. * Relapsed- having relapsed following treatment with at least 1 prior purine-analog treatments
  12. * Participants must be BRAF WT as confirmed from fresh bone marrow aspirate and/or peripheral blood sample, or lymph node/mass by the Laboratory of Pathology, NCI
  13. * 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
  14. * Age greater than or equal to 18 years
  15. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent).
  16. * Adequate organ and marrow function as defined below:
  17. * Total bilirubin less than or equal to 3x upper limit of normal (ULN), unless consistent with Gilbert s (ratio between total and direct bilirubin \> 5)
  18. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3x ULN
  19. * Alkaline phosphatase \<= 5x ULN
  20. * Serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal calculated using estimated glomerular filtration rate (eGFR)
  21. * Serum albumin greater than or equal to 2 g/dL
  22. * Prothrombin time (PT)/International Normalized Ratio (INR) \< 2.5x ULN (If on warfarin, PT/INR \< 3.5x ULN; If on any other anticoagulation, Prothrombin time (PT) \< 2.5x ULN
  23. * Fibrinogen greater than or equal to 0.5x lower limit of normal
  24. * The effects of binimetinib on the developing human fetus are unknown therefore participants must use effective methods of contraception as directed below.
  25. * 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 binimetinib. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. 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. Female subjects must use a hormonal method in addition to a barrier method alone, to minimize the chance of pregnancy. 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.
  26. * Non-sterilized male participants who are sexually active with a female partner of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, and not donate sperm from study entry until 90 days after the last dose of binimetinib.
  27. * Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 days after the last dose of the study drug.
  28. * Ability of participant to understand and the willingness to sign a written informed consent document.
  29. * 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 or radiotherapy within 2 weeks prior to the start of study treatment.
  2. * Prior therapy with 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 its excipients.
  6. * Inability to swallow and retain study drug.
  7. * Pregnant women as evaluated by a positive serum or urine beta-human chorionic gonadotropin (beta-hCG) test.
  8. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac disfunction (details as below), uncontrolled pulmonary infection, pulmonary edema or psychiatric illness/social situations that would limit compliance with study requirements.
  9. * Evidence of active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection.
  10. * Active second malignancy requiring treatment other than minor resection of indolent cancers like basal cell and squamous skin cancers.
  11. * 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.
  12. * History of an allogeneic bone marrow or stem cell transplant.
  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) \< 3 months 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 percent 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 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.
  21. * Concurrent neuromuscular disorder that is associated with elevated creatinine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  22. * 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

Contacts and Locations

Study Contact

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

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 Date2021-01-07
Study Completion Date2028-07-31

Study Record Updates

Study Start Date2021-01-07
Study Completion Date2028-07-31

Terms related to this study

Keywords Provided by Researchers

  • MEK1
  • Inhibitor
  • MEK2
  • MEK162

Additional Relevant MeSH Terms

  • Hairy Cell Leukemia