Actively Recruiting
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
Led by Therapeutic Advances in Childhood Leukemia Consortium · Updated on 2026-04-15
58
Participants Needed
19
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and effectiveness of combining trametinib and azacitidine in children and young adults newly diagnosed with juvenile myelomonocytic leukemia (JMML). This study focuses on two groups: lower-risk patients and high-risk patients, defined by specific genetic and molecular features. The trial aims to determine how well these drug combinations work and their safety in treating JMML. Lower-risk patients will receive daily azacitidine for five days combined with daily trametinib for 28 days per treatment cycle, for up to twelve cycles. High-risk patients will receive a combination of azacitidine, fludarabine, and cytarabine for five days along with daily trametinib for 28 days per cycle, for up to two cycles. These treatments are given through oral and intravenous methods, depending on the drug, and are tailored to the patient's risk category. Participants will undergo evaluations to monitor safety and treatment effects during and after each treatment cycle. Assessments include blood tests, genetic studies, kidney, liver, and heart function checks, and monitoring for side effects. The study will measure safety outcomes at the end of the first treatment cycle plus 30 days. Patients are followed throughout treatment courses lasting up to twelve cycles for lower-risk or two cycles for high-risk JMML, with ongoing monitoring to ensure their well-being.
CONDITIONS
Brief Title
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must be between 1 month and 21 years old at enrollment.
- Diagnosis of juvenile myelomonocytic leukemia (JMML) based on 2022 International Consensus Classification criteria.
- Presence of clinical features including peripheral blood monocyte count ≥ 1 × 10^9/L and splenomegaly.
- Blast percentage in peripheral blood and bone marrow less than 20%.
- Absence of BCR::ABL1 fusion gene.
- Genetic confirmation including somatic mutation in PTPN11, KRAS, NRAS, RRAS, RRAS2 or diagnosis of neurofibromatosis type 1 or CBL syndrome.
- Karnofsky performance status > 50% for patients 16 years and older; Lansky performance status > 50% for patients younger than 16.
- No prior leukemia-directed therapy except limited cytoreduction with hydroxyurea or 6-mercaptopurine within specified time frames.
- Adequate kidney function as defined by creatinine clearance or age/gender-based serum creatinine levels.
- Adequate liver function with bilirubin and ALT levels below specified limits or waiver if liver involvement by leukemia.
- Adequate cardiac function with ejection fraction ≥ 50%.
- Female patients of childbearing potential must have a negative pregnancy test and agree not to breastfeed during the study.
- Agreement to use effective contraception during the study and for six months after treatment.
You will not qualify if you...
- Known allergy to trametinib, azacitidine, fludarabine, or cytarabine.
- Active systemic infections without improvement despite treatment.
- Planned non-protocol chemotherapy, radiation therapy, or immunotherapy during the study.
- Significant concurrent medical, psychiatric, or social conditions compromising safety or compliance.
- Diagnosis of Noonan syndrome.
- Prior use of hematopoietic growth factors, biologics, or radiation therapy.
- Use of medications for left ventricular systolic dysfunction.
- History or current evidence of retinal vein occlusion or central serous retinopathy.
- Prior use of any MEK inhibitor.
- Patients with Down syndrome are excluded.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 12 courses for lower-risk patients; up to 2 courses for high-risk patients
Participants receive treatment based on their risk classification. Lower-risk patients take daily azacitidine for 5 days combined with daily trametinib for 28 days per course, up to 12 courses. High-risk patients receive daily azacitidine, fludarabine, and cytarabine for 5 days combined with daily trametinib for 28 days per course, up to 2 courses.
Repeated visits during each 28-day treatment cycle
Trial Site Locations
Total: 19 locations
1
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
Actively Recruiting
2
Children's Hospital Los Angeles
Los Angeles, California, United States, 900027
Actively Recruiting
3
University of California San Francisco
San Francisco, California, United States, 94158
Actively Recruiting
4
Children's Hospital of Colorado
Denver, Colorado, United States, 80045
Actively Recruiting
5
Children's National Medical Center
Washington D.C., District of Columbia, United States, 20010
Actively Recruiting
6
University of Miami
Miami, Florida, United States, 33136
Actively Recruiting
7
Children's Hospital of Atlanta
Atlanta, Georgia, United States, 30322
Actively Recruiting
8
Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
Actively Recruiting
9
Indiana University/Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
Actively Recruiting
10
Sidney Kimmel Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Actively Recruiting
11
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Actively Recruiting
12
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Actively Recruiting
13
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
14
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Actively Recruiting
15
Oregon Health & Science University
Portland, Oregon, United States, 97239
Actively Recruiting
16
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
17
St. Jude Children's Research Hospital Memphis
Memphis, Tennessee, United States, 38105
Actively Recruiting
18
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
Actively Recruiting
19
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Actively Recruiting
Research Team
E
Ellynore Florendo
S
Suganya Rajendran
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here