Ignite Creation Date:
2024-05-06 @ 2:27 PM
Last Modification Date:
2024-10-26 @ 1:31 PM
Study NCT ID:
NCT04322383
Status:
RECRUITING
Last Update Posted:
2024-06-05
First Post:
2020-03-25
Brief Title:
Binimetinib for People With RelapsedRefractory BRAF Wild Type Hairy Cell Leukemia and Variant
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase 2 Trial for Binimetinib for Patients With RelapsedRefractory BRAF Wild Type Hairy Cell Leukemia and Variant
Status:
RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
Detailed Description:
Background
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 HCLHCLv Furthermore with poor survival outcomes in this patient population lack of targeted therapy constitutes a clear unmet need
Recently several BRAF WT HCLHCLv 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 HCLHCLv patients but MEK inhibition may be clinically useful even in these patients without known MAP2K1 MEK mutations
Objective
-To determine the overall response rate ORR to binimetinib in participants with BRAF WT HCL and HCLv
Eligibility
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 x103mcL Hgb 10gdL Platelet count 100 x103mcL leukemia cell count 5 x103mcL symptomatic splenomegaly enlarging HCL mass 2cm in short axis
-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
Single arm phase 2 trial to determine ORR in participants with relapsedrefractory 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 participants will be enrolled If 2 or more achieve a major response then accrual will continue to a total of 31 evaluable participants
Binimetinib will be given 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 PRCR 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
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 HCLHCLv Furthermore with poor survival outcomes in this patient population lack of targeted therapy constitutes a clear unmet need
Recently several BRAF WT HCLHCLv 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 HCLHCLv patients but MEK inhibition may be clinically useful even in these patients without known MAP2K1 MEK mutations
Objective
-To determine the overall response rate ORR to binimetinib in participants with BRAF WT HCL and HCLv
Eligibility
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 x103mcL Hgb 10gdL Platelet count 100 x103mcL leukemia cell count 5 x103mcL symptomatic splenomegaly enlarging HCL mass 2cm in short axis
-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
Single arm phase 2 trial to determine ORR in participants with relapsedrefractory 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 participants will be enrolled If 2 or more achieve a major response then accrual will continue to a total of 31 evaluable participants
Binimetinib will be given 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 PRCR 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20-C-0075 | None | None | None |