Trametinib and Azacitidine for Juvenile Myelomonocytic Leukemia (JMML)
This study is testing the safety of combining two drugs, trametinib and azacitidine, for children and young adults (ages 1 month to 21 years) who have been newly diagnosed with Juvenile Myelomonocytic Leukemia (JMML). Some patients will also receive fludarabine and cytarabine. The study aims to see how safe these drug combinations are. To join, patients must meet specific criteria for JMML. The study is looking for 58 participants. We don't know the current enrollment status.
- Study design
- This is an interventional study planning to enroll 58 participants. It is testing different drug combinations for lower-risk and high-risk JMML.
- What's involved
- Patients with lower-risk JMML will receive daily azacitidine for 5 days and daily trametinib for 28 days per course, for up to 12 courses. Patients with high-risk JMML will receive daily azacitidine, fludarabine, and cytarabine for 5 days, and daily trametinib for 28 days per course, for up to 2 courses.
- Compensation
- Not stated in the trial record.
- Follow-up
- Safety will be measured at the end of the evaluation period of Cycle 1, which is 28 days of therapy plus 30 days following the last dose.
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NCT05849662
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia
Recruiting
PHASE1Ages 1–21InterventionalTreatmentTherapeutic Advances in Childhood Leukemia ConsortiumInvestigator-initiated
~58 participants
Updated 2026-04-15 on ClinicalTrials.gov
What's tested:TrametinibAzacitidineFludarabineCytarabine
At a glance
Recruiting sites
19 of 19 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
To determine the safety of combining trametinib with azacitidine for patients with newly diagnosed lower-risk JMML.
Measured over 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)
+1 more outcome measured
Conditions
Where it's being run
19 sites across 18 statesCalifornia2
Arizona1
Colorado1
District of Columbia1
Florida1
Georgia1
Illinois1
Indiana1
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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.
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 to be excluded. §Occasional cases with heterozygous splice site mutations.
Karnofsky \> 50% for patients ≥ 16 years of age
Lansky \> 50% for patients \< 16 years of age.
No prior leukemia directed therapy is permitted with the exception of:
Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender in the chart below:
1 month to \< 6 months old - Male: 0.4, Female 0.4
6 months to \<1 year old - Male 0.5, Female 0.5
1 to \< 2 years old - Male: 0.6, Female: 0.6
2 to \< 6 years old - Male:0.8, Female: 0.8
6 to \< 10 years old - Male: 1, Female: 1
10 to \< 13 years old - Male: 1.2, Female: 1.2
13 to \< 16 years old - Male: 1.5, Female: 1.4
≥ 16 years old - Male: 1.7, Female: 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
Direct bilirubin \< 1.5 x upper limit of normal (ULN) for age or normal, AND alanine transaminase (ALT) \< 5 x ULN for age.
The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia and will not be evaluable for hepatotoxicity. This must be reviewed and approved by the study chair or vice chair.
Ejection fraction of \> or = to 50% by echocardiogram, OR
Ejection fraction of \> or = to 50% by radionuclide angiogram (MUGA).
Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.
Female patients with infants must agree not to breastfeed their infants while on this study.
Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
Exclusion
Patients cannot have a known allergy to any of the drugs used in the study.
Patients cannot have a systemic fungal, bacterial, viral, or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
Patients cannot have a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
Patients cannot have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
Patients cannot have a clinical or molecular diagnosis of Noonan syndrome. Note: patients with either neurofibromatosis type 1 or Casitas B-lineage lymphoma (CBL) syndrome (also known as Noonan-like syndrome), are eligible to enroll. Patients with Down syndrome are excluded from the study.
Patient cannot have had prior use of hematopoietic growth factors, biologics (anti-neoplastic agent), or XRT.
Patients cannot be taking any medications for treatment of left ventricular systolic dysfunction.
Patients cannot have a history of or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
Patients cannot have had prior use of any MEK inhibitor.
What this trial measures
- To determine the safety of combining trametinib with azacitidine for patients with newly diagnosed lower-risk JMML.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.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.