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)
Therapeutic Advances in Childhood Leukemia Consortium
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.
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 f…
Eligibility
- Age range
- 0–21 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Age • Patients must be ≥ 1 month and ≤21 years of age at enrollment. Diagnosis • Patients must meet the 2022 International Consensus Classification criteria for JMML. The diagnosis is made based on the following criteria:. Clinical and hematologic features (the first 2 features are present in most cases; the last 2 are required): * Peripheral blood monocyte count ≥ 1 × 109/L\* * Splenomegaly† * Blast percentage in PB and BM \< 20% * Absence of BCR::ABL1 * This monocyte threshold is not reached in approximately 7% of cases. †Splenomegaly is absent in 3% of cases at p…
Interventions
- DrugTrametinib
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
- DrugAzacitidine
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
- DrugFludarabine
IV over 30 minutes Days 6-10 30 mg/m2/day (1mg/kg if \<12 kg)
- DrugCytarabine
IV over 3 hours Days 6-10 2000 mg/m2/day (67mg/kg if \<12 kg)
Locations (19)
- Phoenix Children's HospitalPhoenix, Arizona
- Children's Hospital Los AngelesLos Angeles, California
- University of California San FranciscoSan Francisco, California
- Children's Hospital of ColoradoDenver, Colorado
- Children's National Medical CenterWashington D.C., District of Columbia
- University of MiamiMiami, Florida