A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia
Trial Parameters
Brief 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.
Eligibility Criteria
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 presentation. II. Genetic studies (1 finding required): * Somatic mutation in PTPN11‡ or KRAS‡ or NRAS‡ or RRAS or RRAS2‡ * Clinical diagnosis of neurofibromatosis type 1 or germline NF1 mutation and loss of heterozygosity of NF1 or somatic biallelic loss of NF1 * Germline CBL mutation and loss of heterozygosity of CBL, or somatic mutation(s) in CBL§ * Germline mutations (indicating Noonan syndrome) need t