Trametinib for Juvenile Myelomonocytic Leukemia

Not currently recruiting at 60 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Investigational drugs

Disqualifiers: Pregnancy, Breastfeeding, Uncontrolled infection, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 28

Duration: 12 cycles (1 cycle = 28 days)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of trametinib, a medication, for patients with juvenile myelomonocytic leukemia (JMML) that has either relapsed or does not respond to existing treatments. The focus is on trametinib's ability to halt cancer cell growth. The trial is suitable for patients diagnosed with relapsed or treatment-resistant JMML who have undergone prior therapy. Participants will take trametinib daily in 28-day cycles, with regular checks, such as bone marrow tests, to monitor progress. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. You cannot be on other anti-cancer agents, investigational drugs, or medications for preventing organ rejection. If you are on corticosteroids, you must be on a stable or decreasing dose for at least 7 days before enrolling. Hydroxyurea can be continued until 24 hours before starting the trial treatment.

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

Research has shown that trametinib is safe for young children with juvenile myelomonocytic leukemia (JMML), particularly for those with recurrent or difficult-to-treat disease. In studies, patients generally tolerated trametinib well, indicating it caused few problems. Specifically, one study found that half of the patients responded well to the treatment. While some side effects may occur, they are usually manageable. Overall, trametinib is considered effective and safe for these young patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Trametinib is unique because it targets a specific pathway in the cells that contribute to the growth of juvenile myelomonocytic leukemia (JMML). Unlike traditional chemotherapy, which attacks all rapidly dividing cells, trametinib specifically inhibits MEK, a protein involved in cell division and growth. This targeted approach may result in fewer side effects and better outcomes for patients. Researchers are excited about trametinib because it offers a more precise method of treatment that might improve the quality of life and effectiveness for children with JMML.

What evidence suggests that trametinib might be an effective treatment for juvenile myelomonocytic leukemia?

Research has shown that trametinib, which participants in this trial will receive, holds promise for treating juvenile myelomonocytic leukemia (JMML), especially when the disease recurs or resists other treatments. In studies, trametinib led to a clear improvement in about 50% of patients. Additionally, around 70% of these patients successfully underwent a stem cell transplant or completed their treatment cycles. This is significant for a disease that typically has low survival rates. Overall, trametinib has proven safe and effective for young patients with this challenging condition. ^{1 2 5 6 7}

Who Is on the Research Team?

Elliot Stieglitz

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients under 22 years with juvenile myelomonocytic leukemia (JMML) that's relapsed or not responding to treatment. They must have recovered from previous treatments, be able to swallow pills, and meet specific health criteria like heart function and normal blood levels.

Inclusion Criteria

I am between 1 month and 22 years old.

My leukemia (JMML) has come back or is not responding to treatment.

I can do most activities but may need help.

Exclusion Criteria

Patients with a history of allergic reaction attributed to compounds of similar chemical or biologic composition to the MEK inhibitor, trametinib

I am taking medication to prevent organ rejection after a transplant.

I have had a liver condition called sinusoid obstructive syndrome in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trametinib orally once daily on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles.

12 cycles (1 cycle = 28 days)

Bone marrow aspiration or biopsy at baseline, day 28 of cycles 1 and 2, all subsequent odd numbered cycles, and end of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Annually for up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Trametinib

Trial Overview The study tests trametinib effectiveness in treating JMML that has returned or is refractory. Trametinib aims to halt tumor growth by inhibiting enzymes necessary for cell proliferation. The process includes bone marrow procedures alongside medication administration.

How Is the Trial Designed?

Group I: Treatment (trametinib) Experimental Treatment 2 Interventions

Patients receive trametinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a bone marrow aspiration or biopsy at baseline, on day 28 of cycles 1 and 2, at all subsequent odd numbered cycles, and at end of treatment.

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

Approved in European Union as Mekinist for:

• Melanoma
• Non-small cell lung cancer

Approved in United States as Mekinist for:

• Melanoma
• Non-small cell lung cancer
• Thyroid cancer

Approved in Canada as Mekinist for:

• Melanoma
• Non-small cell lung cancer

Approved in Japan as Mekinist for:

• Melanoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Published Research Related to This Trial

Chronic myelomonocytic leukemia (CMML) shows increased sensitivity of myeloid progenitors to granulocyte macrophage-colony stimulating factor, indicating a need for targeted therapies.

Ruxolitinib, a JAK1 and JAK2 inhibitor, has been demonstrated to induce objective responses in patients with CMML, suggesting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unplugging JAK/STAT in Chronic Myelomonocytic Leukemia. Solary, E.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38867349/

Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed ... Trametinib was safe and effective in young children with relapsed or refractory JMML, a lethal disease with poor survival rates.

2. aacrjournals.org aacrjournals.org/cancerdiscovery/article/14/9/1590/747380/Efficacy-of-the-Allosteric-MEK-Inhibitor

Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed ... Significance: Trametinib was safe and effective in young children with relapsed or refractory JMML, a lethal disease with poor survival rates. Seven of 10 ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/74/499342/Efficacy-of-the-Allosteric-MEK-Inhibitor

Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed ... The trial met its primary objective and demonstrated a 50% objective response rate with 70% of patients bridging to a successful HSCT or completing the maximum ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03190915

Study Details | NCT03190915 | Trametinib in Treating ... This phase II trial studies how well trametinib works in treating patients with juvenile myelomonocytic leukemia that has come back (relapsed) or does not ...

5. aacr.org aacr.org/about-the-aacr/newsroom/news-releases/trametinib-shows-promise-for-children-with-relapsed-or-refractory-jmml/

Trametinib Shows Promise for Children with Relapsed or ... The MEK inhibitor trametinib (Mekinist) was an effective treatment for pediatric patients with relapsed or refractory juvenile myelomonocytic leukemia (JMML)

6. ashpublications.org ashpublications.org/thehematologist/article/doi/10.1182/hem.V21.2.202427/515055/Risk-stratified-Treatment-for-Pediatric-Patients

Risk-stratified Treatment for Pediatric Patients With Newly ... Patients with lower-risk JMML will be treated with azacitidine for five days in combination with trametinib for 28 days per course for up to 12 courses.

7. hematologyadvisor.com hematologyadvisor.com/news/trametinib-safe-effective-for-juvenile-myelomonocytic-leukemia/

Trametinib Safe, Effective for Juvenile Myelomonocytic ... The researchers found that the objective response rate was 50 percent. After receiving trametinib, four patients with refractory disease ...