NCT05849662 · Therapeutic Advances in Childhood Leukemia Consortium
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia
What this study is about
This clinical trial will test the safety and effectiveness 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.
View original scientific description
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.
Interventions
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)
Primary outcome measures
To determine the safety of combining trametinib with azacitidine for patients with newly diagnosed lower-risk JMML.
Time frame: At the end of the evaluation period of Cycle 1 (defined as 28 day cycle of therapy plus 30 days following the last dose of study therapy)
The incidence of dose limiting toxicities (DLTs) after the 1st course of therapy will be measured at different dose levels.
To determine the safety of combining trametinib with azacitidine (Aza), fludarabine (FLA) and cytarabine for patients with newly diagnosed high-risk JMML.
Time frame: At the end of the evaluation period of Cycle 1 (defined as 28 day cycle of therapy plus 30 days following the last dose of study therapy)
The incidence of dose limiting toxicities (DLTs) after the 1st course of therapy will be measured at different dose levels.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 syn
Where
- Phoenix, Arizona
- Los Angeles, California
- San Francisco, California
- Denver, Colorado
- Washington D.C., District of Columbia
- Miami, Florida
- Atlanta, Georgia
- Chicago, Illinois
- Indianapolis, Indiana
- Baltimore, Maryland
- Ann Arbor, Michigan
- Kansas City, Missouri
And 7 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 15, 2026 · Source of record for eligibility and locations