NCT05849662

A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia

Risk Stratified Treatment for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia: A Phase I/II Non-randomized Study of Trametinib and Azacitidine With or Without Chemotherapy (IND #164058)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 58 (estimated)
• Sponsor: Therapeutic Advances in Childhood Leukemia Consortium · Academic / Other
• Sex: All
• Age: 1 Month – 21 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial will test the safety and efficacy of combining trametinib and azacitidine in patients with juvenile myelomonocytic leukemia (JMML). Newly diagnosed lower-risk JMML patients will receive trametinib and azacitidine. High-risk JMML patients will receive trametinib, azacitidine, fludarabine, and cytarabine.

Detailed description

Primary Objectives: 1. To determine the safety of combining trametinib with azacitidine for patients with newly diagnosed lower-risk JMML. 2. To determine the safety of combining trametinib with azacitidine (Aza), fludarabine (FLA) and cytarabine for patients with newly diagnosed high-risk JMML. Dosing: Patients with newly diagnosed lower-risk JMML will be treated with daily azacitidine for 5 days in combination with daily trametinib for 28 days per course for up to 12 courses. Patients with newly diagnosed high-risk JMML will be treated with daily azacitidine, fludarabine, and cytarabine for 5 days in combination with daily trametinib for 28 days per course for up to 2 courses.

Conditions

• Leukemia, Juvenile Myelomonocytic
• JMML
• JCML
• Neurofibromatosis 1
• CBL Syndrome

Interventions

Type	Name	Description
DRUG	Trametinib	PO or NG QD Days 1-28 For patients age \< 6 years: 0.032 mg/kg/day at max dose = 2mg/day For patients age ≥ 6 years: 0.025 mg/kg/day at max dose = 2 mg/day
DRUG	Azacitidine	IV over 30 minutes Days 1-5 Age \< 1 year or weight \<10kg: 2.5 mg/kg/day Age ≥ 1 year and weight ≥ 10kg: 75 mg/m2/day
DRUG	Fludarabine	IV over 30 minutes Days 6-10 30 mg/m2/day (1mg/kg if \<12 kg)
DRUG	Cytarabine	IV over 3 hours Days 6-10 2000 mg/m2/day (67mg/kg if \<12 kg)

Timeline

• Start date: 2024-10-11
• Primary completion: 2028-12-01
• Completion: 2029-12-01
• First posted: 2023-05-09
• Last updated: 2026-04-15

Locations

19 sites across 1 country: United States

Regulatory

• FDA-regulated drug study