Binimetinib for Hairy Cell Leukemia

Overseen By Holly Eager (DiFebo), R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Chemotherapy, Immunotherapy, Radiotherapy, others

Disqualifiers: Pregnancy, Active infection, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Ongoing 28-day cycles

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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. ...

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have had chemotherapy, immunotherapy, or radiotherapy within 4 weeks before starting the study treatment, or if you are currently taking other investigational agents.

Is Binimetinib (Mektovi) generally safe for humans?

The safety of Binimetinib (Mektovi) has been evaluated in other conditions, and it is known to cause some side effects, such as skin issues, when used as part of BRAF inhibitor therapy. However, specific safety data for its use in hairy cell leukemia is not provided in the available research. ^{1 2 3 4 5}

How is the drug Binimetinib unique for treating Hairy Cell Leukemia?

Binimetinib is unique for treating Hairy Cell Leukemia because it is a MEK inhibitor, which targets a specific pathway in cancer cells, potentially offering a new approach compared to traditional chemotherapy or other treatments that do not specifically target this pathway. ^{6 7 8 9 10}

Research Team

Robert J Kreitman, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with hairy cell leukemia that doesn't have the BRAF gene mutation, who've had their disease return or not respond to treatment. They must have certain blood count levels and organ function, agree to use contraception, and be willing to sign consent. Excluded if recently treated with other therapies, pregnant/breastfeeding, uncontrolled illnesses, active infections like HBV/HCV or HIV without proper control.

Inclusion Criteria

My liver, kidney, and blood functions meet the required levels for the trial.

My disease did not improve or worsened within a year after treatment, or it came back after treatment.

I cannot or do not want to participate in the Moxetumomab Pasudotox trial.

Exclusion Criteria

I cannot swallow or keep down the medication.

I have heart problems or significant heart disease.

Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants take binimetinib by mouth twice daily in 28-day cycles. They will have at least one visit before every cycle, including repeats of some screening tests.

Ongoing 28-day cycles

1 visit per cycle (in-person)

Follow-up

About a month after their last dose of treatment, participants will have a follow-up visit. They will then have visits once a year.

1 month after treatment, then annually

1 visit (in-person) after treatment, annual visits

Treatment Details

Interventions

• Binimetinib

Trial Overview The trial is testing binimetinib—a MEK inhibitor—on participants taking it orally twice daily in cycles of 28 days. It's for those whose leukemia lacks a BRAF mutation and aims to see if this drug can effectively treat their condition when other treatments haven't worked.

Participant Groups

Group I: Arm 1/Experimental therapy Experimental Treatment 1 Intervention

Treatment with binimetinib

Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in European Union as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Approved in Canada as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in Japan as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The BRAF V600E mutation is a key genetic marker in hairy cell leukemia (HCL), influencing both diagnosis and treatment options, particularly with BRAF inhibitors.

Clinical reports and phase 2 trials suggest that BRAF inhibitors can be effective for treating relapsed or refractory HCL, although they may cause side effects like skin toxicity, highlighting the need for careful management and potential combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAF in the cross-hairs. Geyer, MB., Abdel-Wahab, O., Tallman, MS.[2020]

Bendamustine-rituximab (BR) treatment showed a 100% overall response rate in patients with multiply relapsed/refractory hairy cell leukemia, with significant complete remission rates of 50% and 67% for the 70 mg/m² and 90 mg/m² dose groups, respectively.

The treatment was well-tolerated, with no significant dose-related differences in efficacy or toxicity, and the 90 mg/m² dose was selected for future studies due to its effectiveness and manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. Burotto, M., Stetler-Stevenson, M., Arons, E., et al.[2022]

In a study of 123 patients with hairy cell leukemia (HCL) diagnosed between 1996 and 2016, cladribine as a first-line treatment resulted in a high hematological complete response rate of 92%, demonstrating its efficacy in managing this rare cancer.

The median overall survival for HCL patients was over 15 years, with 5-year and 10-year survival rates of 84% and 70.5%, indicating a favorable long-term prognosis, especially compared to other treatments like IFN-α which had a higher relapse rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A population-based study of hairy cell leukemia over a period of 20 years. Wiber, M., Maitre, E., Poncet, JM., et al.[2021]

The survival rates for patients with hairy cell leukemia (HCL) have improved significantly due to effective treatments like interferon alpha and purine analogs, but these treatments may increase the risk of developing secondary cancers, particularly acute leukemia.

In a unique case, a patient developed acute myeloid leukemia (AML) just 1.2 years after HCL diagnosis and treatment, which is notably earlier than the average 4.3 years reported in other cases, suggesting a potential link between HCL treatments and the onset of secondary leukemias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia following treatment with cladribine for hairy cell leukemia: a case report and review of the literature. Hassan, R., Gupta, M., Kern, W., et al.[2019]

BRAF and MEK inhibitors, such as vemurafenib and trametinib, effectively target the BRAF-V600E mutation in hairy cell leukemia (HCL), leading to significant dephosphorylation of the MEK/ERK pathway and inducing apoptosis in leukemic cells from 26 patients.

The study highlights that combining BRAF and MEK inhibitors can overcome protective effects from bone marrow stromal cells, suggesting a promising therapeutic strategy for improving treatment outcomes in HCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity. Pettirossi, V., Santi, A., Imperi, E., et al.[2022]

Imatinib mesylate (STI571) has been approved by the FDA as an effective treatment for chronic myeloid leukemia (CML) after failure of or withdrawal from interferon-alfa, marking a significant advancement in therapy over previous treatments.

Allogeneic stem cell transplantation remains a potential cure for about 20% of CML patients, but the introduction of imatinib has prompted a reevaluation of its role in treatment strategies, highlighting the importance of targeted therapies in managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic strategies for chronic myeloid leukemia in the chronic (stable) phase. Goldman, JM.[2015]

Imatinib Mesylate has significantly improved outcomes for chronic myeloid leukemia (CML) patients in the chronic phase, leading to high rates of complete hematologic and cytogenetic responses.

Long-term studies indicate that while Imatinib is effective, there is a need for early molecular markers to identify which patients will benefit most from this treatment, especially with the availability of generic options and newer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes. Stagno, F., Stella, S., Spitaleri, A., et al.[2016]

A 64-year-old man with limited cutaneous systemic sclerosis and newly diagnosed chronic myelogenous leukemia (CML) showed significant improvement in both conditions after starting dasatinib therapy, achieving a complete cytogenetic response in CML within 6 months.

This case suggests that dasatinib may not only effectively treat CML but also lead to substantial improvement in skin symptoms associated with systemic sclerosis, indicating a potential dual benefit that warrants further investigation into its mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib for chronic myelogenous leukemia improves skin symptoms of systemic sclerosis. Arai, K., Yoshifuji, K., Motomura, Y., et al.[2020]

Targeted therapy with tyrosine kinase inhibitors (TKIs) like ponatinib has significantly improved survival rates for patients with Chronic Myeloid Leukemia (CML), bringing them close to those of age-matched controls.

Ponatinib is effective against both early and advanced phases of CML, including cases with the resistant T315I mutation, but its use requires careful consideration of potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ponatinib in the therapy of chronic myeloid leukemia. Poch Martell, M., Sibai, H., Deotare, U., et al.[2017]

Chronic myeloid leukemia (CML) has been a key model for cancer research, particularly due to the successful targeting of the BCR-ABL tyrosine kinase with the drug imatinib, which has led to significant remissions in patients.

The success of imatinib in CML has spurred the development of targeted therapies for other cancers, with many new inhibitors currently being tested in clinical trials worldwide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic myeloid leukemia: a model for oncology. Hehlmann, R., Berger, U., Hochhaus, A.[2007]

References

1. England pubmed.ncbi.nlm.nih.gov

BRAF in the cross-hairs. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A population-based study of hairy cell leukemia over a period of 20 years. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia following treatment with cladribine for hairy cell leukemia: a case report and review of the literature. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Therapeutic strategies for chronic myeloid leukemia in the chronic (stable) phase. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes. [2016]

8. Japan pubmed.ncbi.nlm.nih.gov

Dasatinib for chronic myelogenous leukemia improves skin symptoms of systemic sclerosis. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Ponatinib in the therapy of chronic myeloid leukemia. [2017]

10. Germany pubmed.ncbi.nlm.nih.gov

Chronic myeloid leukemia: a model for oncology. [2007]