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

Recruiting now · Phase 1/Phase 2

Conditions studied: Leukemia, Juvenile Myelomonocytic, JMML, JCML, Neurofibromatosis 1, CBL Syndrome

In brief

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.

Key facts

Study ID: NCT05849662
Run by: Therapeutic Advances in Childhood Leukemia Consortium
People needed: 58
Starts: 2024-10-11
Expected to finish: 2029-12-01
Last updated by the study team: 2026-04-15

Who can join

Age: 0 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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 to be excluded. §Occasional cases with heterozygous splice site mutations.
Performance Level
Karnofsky > 50% for patients ≥ 16 years of age
Lansky > 50% for patients < 16 years of age.
Prior Therapy
No prior leukemia directed therapy is permitted with the exception of:
Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of trametinib.
Cytoreduction with 6-mercaptopurine (6-MP) 6-MP can be initiated and continued for up to 72 hours prior to the start of trametinib.
Intrathecal (IT) cytarabine, IT methotrexate or triple IT therapy (cytarabine, methotrexate and hydrocortisone) within 7 days of enrollment as part of a diagnostic evaluation.
No prior hematopoietic stem cell transplant is permitted.
Adequate Renal Function Defined as:
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:

You may not qualify if…

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.

Where it is running

Phoenix Children's Hospital — Phoenix, Arizona, United States (enrolling)
Children's Hospital Los Angeles — Los Angeles, California, United States (enrolling)
University of California San Francisco — San Francisco, California, United States (enrolling)
Children's Hospital of Colorado — Denver, Colorado, United States (enrolling)
Children's National Medical Center — Washington D.C., District of Columbia, United States (enrolling)
University of Miami — Miami, Florida, United States (enrolling)
Children's Hospital of Atlanta — Atlanta, Georgia, United States (enrolling)
Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (enrolling)
Indiana University/Riley Hospital for Children — Indianapolis, Indiana, United States (enrolling)
Sidney Kimmel Cancer Center at Johns Hopkins — Baltimore, Maryland, United States (enrolling)
C.S. Mott Children's Hospital — Ann Arbor, Michigan, United States (enrolling)
Children's Mercy Hospital — Kansas City, Missouri, United States (enrolling)
Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (enrolling)
Oregon Health & Science University — Portland, Oregon, United States (enrolling)
Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (enrolling)
St. Jude Children's Research Hospital Memphis — Memphis, Tennessee, United States (enrolling)
Primary Children's Hospital — Salt Lake City, Utah, United States (enrolling)
Seattle Children's Hospital — Seattle, Washington, United States (enrolling)

Full record on ClinicalTrials.gov

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