Trametinib for Juvenile Myelomonocytic Leukemia

Recruiting at 57 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)

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well trametinib works in treating patients with juvenile myelomonocytic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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.

What data supports the effectiveness of the drug Trametinib for treating Juvenile Myelomonocytic Leukemia?

Research shows that combining Trametinib, a MEK inhibitor, with other treatments like 5-azacitidine can help reduce leukemia-related issues in a mouse model of Juvenile Myelomonocytic Leukemia. Additionally, two patients with specific genetic mutations in JMML showed positive responses when treated with Trametinib, 5-azacitidine, and chemotherapy. ^{1 2 3 4 5}

How is the drug trametinib unique in treating juvenile myelomonocytic leukemia?

Trametinib is unique because it targets the Ras/MAPK pathway, which is often hyperactivated in juvenile myelomonocytic leukemia due to mutations like PTPN11. This makes it different from traditional chemotherapy, which is not durably effective for this condition. ^{1 2 3 5 6}

Research Team

Elliot Stieglitz

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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.

Patients who are pregnant or breast-feeding

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Tretinoin Enhances the Effects of Chemotherapy in Juvenile Myelomonocytic Leukemia Using an Ex Vivo Drug Sensitivity Assay. [2023]

2. China pubmed.ncbi.nlm.nih.gov

[Clinical features and prognosis of juvenile myelomonocytic leukemia: an analysis of 63 cases]. [2023]

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

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

4. Australia pubmed.ncbi.nlm.nih.gov

Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia. [2019]

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

Potential clinical use of azacitidine and MEK inhibitor combination therapy in PTPN11-mutated juvenile myelomonocytic leukemia. [2023]

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

Phase II/III trial of a pre-transplant farnesyl transferase inhibitor in juvenile myelomonocytic leukemia: a report from the Children's Oncology Group. [2018]