Binimetinib for People With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04322383|
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : March 15, 2021
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.
To see if binimetinib is an effective treatment for hairy cell leukemia that does not have a BRAF mutation.
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
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.
|Condition or disease||Intervention/treatment||Phase|
|Hairy Cell Leukemia||Drug: binimetinib||Phase 2|
- Hairy cell leukemia (HCL) is an indolent B-cell leukemia comprising 2% of all leukemias, or approximately 1900 new cases per year in the US.
- BRAF V600E mutation is very common in classic HCL.
- HCL variant (HCLv) is wild type for BRAF and is more aggressive compared to classic HCL due to its lower response and shorter duration of response to standard purine analog chemotherapy. The median survival is only ~6 years compared to >25 years for classic HCL.
- CD25+ classic-appearing HCL-cells that express unmutated IGHV4-34+ immunoglobulin rearrangement, are wild-type for BRAF, and confer a poor prognosis when treated with standard purine analog chemotherapy.
- While BRAF and MEK combination inhibition is making an impact in the treatment of BRAF V600E mutated HCL, this treatment is not applicable for patients with BRAF-WT HCL/HCLv. Furthermore, with poor survival outcomes in this patient population, lack of targeted therapy constitutes a clear unmet need.
- Recently, several BRAF WT HCL/HCLv patients have received MEK inhibitors by compassionate use and have had lifesaving partial to complete remission, however the response has not been assessed systematically in clinical trials.
- Binimetinib (also known as MEK162) is an orally bioavailable, selective and potent mitogenactivated protein (MAP) kinase kinase (MEK1 and MEK2) inhibitor, which is approved for use in combination with encorafenib for the treatment of patients with BRAF-mutant melanoma
- We have described MAP2K1 (MEK) mutations which may drive the aggressive clinical behavior of BRAF WT HCL/HCLv patients, but MEK inhibition may be clinically useful even in these patients without known MAP2K1 (MEK) mutations.
-To determine the overall response rate (ORR) to binimetinib, in patients with BRAF WT HCL and HCLv.
- BRAF WT HCL or HCLv 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 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.
- Single arm phase 2 trial to determine ORR in patients with relapsed/refractory BRAF WT HCL and HCLv.
- 2-phase minimax design will be used to rule out an unacceptable 10% in favor of an improved 25% ORR.
- Initially 16 evaluable patients will be enrolled. If 2 or more achieve a major response, then accrual will continue to a total of 31 evaluable patients.
- Binimetinib will be given at a dose of 45mg BID for as long as patients can continue dosing chronically without significant toxicity.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 2 Trial for Binimetinib for Patients With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant|
|Actual Study Start Date :||January 7, 2021|
|Estimated Primary Completion Date :||April 30, 2024|
|Estimated Study Completion Date :||July 31, 2024|
Experimental: Arm 1/Experimental therapy
Treatment with binimetinib
Binimetinib will be given orally at a dose of 45mg BID continuously for 28- day cycles with no resting period between cycles.
- overall response rate [ Time Frame: every year ]Percentage of patients with the best overall response of CR or PR to therapy
- CR rate [ Time Frame: every year ]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
- Progression free survival [ Time Frame: every year ]duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first
- Overall survival [ Time Frame: every year ]the time from the start of the treatment until time of death from any cause
- time to next treatment [ Time Frame: every year ]duration of time from the start of the binimetinib to next line of treatment
- safety [ Time Frame: every 4 weeks ]The fraction of patients with toxicity noted will be reported by grade and type of toxicity identified.
- different response relative to MAP2K1 mutations [ Time Frame: every year ]determine whether the response to binimetinib is different in patients with and without MAP2K1 (MEK mutations), in patients for which MEK status is known
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04322383
|Contact: Holly Eager, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Robert J Kreitman, M.D.||National Cancer Institute (NCI)|