Mirdametinib for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: BTK inhibitors, BCL2 inhibitors

Must not be taking: P-gp inhibitors, CYP3A4 inducers

Disqualifiers: Pregnancy, Active infection, Glaucoma, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the treatment mirdametinib can help people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that hasn't responded to other treatments or has returned after improvement. Mirdametinib is designed to block signals that promote cancer cell growth, potentially slowing or stopping the disease. It suits those who have tried at least two other treatments for CLL, including a Bruton's tyrosine kinase (BTK) inhibitor, and are experiencing symptoms like severe fatigue, fever, or weight loss. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial requires stopping certain medications that strongly affect specific proteins in the body. If you are taking these, you may need to stop them for a period before starting the trial. It's best to discuss your current medications with the trial team to see if any changes are needed.

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

Research has shown that mirdametinib is generally well-tolerated by patients. Long-term studies have not identified any new safety concerns, confirming its safety over time. More than 25% of patients reported common side effects such as rash, diarrhea, muscle pain, vomiting, nausea, and fatigue. While these side effects are important to consider, they do not suggest serious safety issues. Overall, mirdametinib has a strong safety record, making it a promising option for treating chronic lymphocytic leukemia and small lymphocytic lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic lymphocytic leukemia, which often include chemotherapy and immunotherapy, mirdametinib is unique because it targets a specific pathway involved in cancer cell growth known as the MEK pathway. This precision targeting can potentially lead to fewer side effects and more effective results compared to more generalized treatments. Researchers are excited about mirdametinib because it offers a new approach to slowing down or stopping cancer progression, which could be a game-changer for patients who have not responded well to traditional therapies.

What evidence suggests that mirdametinib might be an effective treatment for chronic lymphocytic leukemia?

Research shows that mirdametinib, a type of medication, can block proteins that signal cancer cells to grow. This may help slow or stop cancer from spreading in people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Participants in this trial will receive mirdametinib to assess its effectiveness in these conditions. Although studies on CLL and SLL are ongoing, mirdametinib has shown promise in other conditions. Specifically, it significantly reduced tumor sizes in patients with neurofibromatosis type 1 (NF1), with an average reduction of about 41-42%. These findings suggest that mirdametinib could be beneficial in treating CLL or SLL, especially for patients whose cancer has returned or did not respond to other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Jennifer R Brown

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that's returned after treatment or hasn't responded to prior therapy can join. They must have certain symptoms like fatigue, fever, weight loss, or enlarged spleen/lymph nodes. Previous treatment with a BTK inhibitor is required.

Inclusion Criteria

* Massive or progressive splenomegaly; OR * Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR * Grade 2 or 3 fatigue; OR * Fever ≥ 100.5°F or night sweats for greater than 2 weeks without documented infection; OR * Presence of weight loss ≥ 10% over the preceding 6 months; OR * Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or an anticipated doubling time of less than 6 months; OR * Evidence of progressive marrow failure as manifested by the development of or worsening of anemia and or thrombocytopenia

I have signs of disease that can be measured, like high lymphocyte count or large lymph nodes.

I am 18 years old or older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirdametinib orally twice daily on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Regular visits for bone marrow biopsy, blood sample collection, echocardiography, and CT

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days, then every 2 months until starting a new therapy, followed by every 3 months for up to a total of 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Mirdametinib

Trial Overview

The trial tests Mirdametinib, which blocks proteins that tell cancer cells to grow, potentially slowing the disease in patients with relapsed/refractory CLL/SLL. It includes biospecimen collection and imaging tests like CT scans and echocardiography.

How Is the Trial Designed?

Group I: Treatment (mirdametinib) Experimental Treatment 5 Interventions

Patients receive mirdametinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow biopsy, blood sample collection, echocardiography, and CT throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07061951

Study Details | NCT07061951 | Testing the Effectiveness of ...

This phase II trial tests the effect of mirdametinib in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that ...

2.

onclive.com

onclive.com/view/dr-hirbe-on-long-term-efficacy-and-safety-outcomes-with-mirdametinib-in-symptomatic-nf1-pn

Dr Hirbe on Long-Term Efficacy and Safety Outcomes With ...

Angela C. Hirbe, MD, PhD, discusses long-term follow-up data from the phase 2b ReNeu trial evaluating mirdametinib in patients with NF1- ...

3.

clin.larvol.com

clin.larvol.com/trial-detail/NCT07061951

Testing the Effectiveness of the Anti-cancer Drug, Mirdametinib ...

Duration of response, Will be summarized descriptively. Up to 5 years ; Overall survival, Up to 5 years ; Incidence of adverse events (AEs), Will be described and ...

4.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT07061951/testing-the-effectiveness-of-the-anti-cancer-drug-mirdametinib-in-treating-relapsed-refractory-chronic-lymphocytic-leukemia?activelyRecruiting=false&page=41&id=745&slug=chronic-lymphocytic-leukemia

Testing the Effectiveness of the Anti-cancer Drug ...

This phase II trial tests the effect of mirdametinib in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma

5.

oncologytube.com

oncologytube.com/fda-approves-mirdametinib-is-this-the-breakthrough-nf1-pn-patients-have-been-waiting-for/

FDA Approves Mirdametinib: Is this the Breakthrough NF1- ...

The drug led to median tumor volume reductions of -41% in adults and -42% in children. Over half of the responders in both groups achieved more ...

6.

gomekli.com

gomekli.com/overview-brochure.pdf

GOMEKLI (mirdametinib) Overview Brochure

Adverse Reactions (>25%) in both adult and pediatric patients include rash, diarrhea, musculoskeletal pain, vomiting, and nausea, as well as fatigue in adult ...

7.

ema.europa.eu

ema.europa.eu/en/documents/rmp/ezmekly-epar-risk-management-plan_en.pdf

European (EU) Risk Management Plan (RMP) for EZMEKLY ...

The nonclinical safety profile of mirdametinib was evaluated in a series of exploratory toxicity studies in rats, dogs, and monkeys, with ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2025/219379Orig1s000,219389Orig1s000MultidisciplineR.pdf

219379Orig1s000 219389Orig1s000 - accessdata.fda.gov

The data from these studies were analyzed together as a single pool and are supportive safety data used to assess the safety profile of mirdametinib. This ...