Binimetinib for Hairy Cell Leukemia

Overseen By Holly M Eager, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if binimetinib (also known as Mektovi), a drug targeting a specific gene mutation, can effectively treat hairy cell leukemia in patients without the common BRAF mutation. Many with this leukemia type cannot use standard treatments without the BRAF mutation, so this trial explores an alternative option. Suitable candidates for this trial are adults with hairy cell leukemia lacking the BRAF mutation, whose disease has not responded to or has returned after previous treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that binimetinib is likely to be safe for humans?

Research shows that binimetinib, a MEK inhibitor, is under study as a treatment for people with hairy cell leukemia who do not have a change in the BRAF gene. Although specific safety information for binimetinib in hairy cell leukemia is not available, it has been tested in other conditions.

In these other studies, binimetinib was generally safe for most people. Some patients experienced side effects, with skin problems being the most common, while serious side effects were less frequent.

As this is a phase 2 trial, earlier studies have found the treatment safe enough to test in more people. However, monitoring for any side effects during the trial remains important. Participants should be aware of possible side effects and discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hairy cell leukemia?

Binimetinib is unique because it targets a specific pathway in cancer cells known as the MAPK/ERK pathway, which is often overactive in hairy cell leukemia. This is different from current treatments like cladribine and pentostatin, which are chemotherapy agents that broadly attack rapidly dividing cells. Researchers are excited about binimetinib because it offers a more targeted approach, which may result in fewer side effects and potentially more effective treatment outcomes. Additionally, as a MEK inhibitor, binimetinib represents a new class of therapy for this condition, offering hope for patients who may not respond well to existing treatments.

What evidence suggests that binimetinib might be an effective treatment for hairy cell leukemia without a BRAF mutation?

Research suggests that binimetinib, a MEK inhibitor, might be a promising treatment for hairy cell leukemia when the BRAF gene remains unchanged. In these cases, the MEK gene often changes, and binimetinib specifically targets this alteration. Although limited data exists on binimetinib's effectiveness for hairy cell leukemia, its mechanism suggests potential benefits. Previous studies on similar medications have shown positive results in related conditions, indicating that targeting the MEK pathway can be effective. Overall, binimetinib could help patients who cannot use BRAF inhibitors. Participants in this trial will receive binimetinib as the experimental therapy. ^{5 6 7 8 9}

Who Is on the Research Team?

Robert J Kreitman, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=20-C-0075&&query=Bone

Protocol Details 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/PO-25-00269

Complete Response in Hairy Cell Leukemia to Anti-CD22 ... In a phase I trial in predominantly B-ALL, anti-CD22 CAR-T cells achieved a CR rate of 70% in 58 patients with a median relapse-free survival of ...

3. withpower.com withpower.com/trial/phase-3-leukemia-hairy-cell-9-2020-1c47b

Encorafenib + Binimetinib for Hairy Cell Leukemia Published Research Related to This Trial ... In a study involving 64 patients with hairy cell leukemia, 89% responded positively to treatment with interferon alfa ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04324112

Encorafenib Plus Binimetinib for People With BRAF V600 ... The nucleoside analogs cladribine and pentostatin are highly active as monotherapy with complete remission (CR) rates of 80 to 90%.

5. hairycellleukemia.org hairycellleukemia.org/may-2024-clinical-trials-nci

HCL Clinical Trials at the National Cancer Institute (NCI)-NIH The BRAF inhibitor dabrafenib alone gives 30% complete remissions in HCL. Dabrafenib and trametinib have been shown to be more effective and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04322383

Study Details | NCT04322383 | Binimetinib for People With ... 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 ...

7. withpower.com withpower.com/trial/phase-3-leukemia-2021-5a507?lat=34.60184&lng=-117.81218

Binimetinib for Hairy Cell Leukemia However, specific safety data for its use in hairy cell leukemia is not provided in the available research. Show more. How is the drug Binimetinib ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ajh.27240

Hairy cell leukemia 2024: Update on diagnosis, risk‐ ... Safety data from the clinical trials either with vemurafenib include as adverse events (AES) and serious adverse events (SAES) skin toxicity ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11610546/

Cell therapy for a rare disease- hairy cell leukemia variant Due to the rarity of HCL-v and paucity of clinical trial data, an accepted treatment regimen has not yet been established for these patients.