New drug combo aims to tame rare childhood leukemia

NCT ID NCT05849662

Disease control Sponsor: Therapeutic Advances in Childhood Leukemia Consortium Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Sep 04, 2026 · Updated 3 times

Summary

This study tests a combination of two drugs, trametinib and azacitidine, for children newly diagnosed with juvenile myelomonocytic leukemia (JMML), a rare blood cancer. Lower-risk patients get just these two drugs, while higher-risk patients also receive standard chemotherapy. The goal is to see if this approach is safe and works better than current treatments. About 58 children and young adults up to age 21 will take part.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: trametinib and azacitidine (with or without fludarabine and cytarabine)
What this could lead to: If successful, this could provide a more effective, risk-adapted treatment for children with JMML, potentially improving survival and reducing side effects.
What could go wrong: This is an early-phase trial with only 58 participants, so results may not apply to all patients. The drug combinations can cause serious side effects like infections and organ damage.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

About 58 people

The number the study aims to enrol. It can still change while the study runs.

Started

Oct 2024

Expected to finish

Dec 2029

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

1 month to 21 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 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: 1. Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of trametinib. 2. Cytoreduction with 6-mercaptopurine (6-MP) 6-MP can be initiated and continued for up to 72 hours prior to the start of trametinib. 3. 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: Maximum Serum Creatinine (mg/dL): * 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. Adequate Liver Function Defined as: * 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. Adequate Cardiac Function Defined as: * Ejection fraction of \> or = to 50% by echocardiogram, OR * Ejection fraction of \> or = to 50% by radionuclide angiogram (MUGA). Reproductive Function * 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 Criteria: * 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.

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Conditions

The condition(s) this trial relates to.

CBL-related disorder juvenile myelomonocytic leukemia neurofibromatosis type 1

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

CBL syndrome JCML JMML Leukemia, juvenile myelomonocytic Neurofibromatosis 1

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

21 sites. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

C.S. Mott Children's Hospital
RECRUITING

Ann Arbor, Michigan, 48109, United States
Children's Hospital Los Angeles
RECRUITING

Los Angeles, California, 900027, United States
Children's Hospital of Atlanta
RECRUITING

Atlanta, Georgia, 30322, United States
Children's Hospital of Colorado
RECRUITING

Denver, Colorado, 80045, United States
Children's Hospital of Philadelphia
RECRUITING

Philadelphia, Pennsylvania, 19104, United States
Children's Medical Center
RECRUITING

Dallas, Texas, 75235, United States
Children's Mercy Hospital
RECRUITING

Kansas City, Missouri, 64108, United States
Children's National Medical Center
RECRUITING

Washington D.C., District of Columbia, 20010, United States
Cincinnati Children's Hospital Medical Center
RECRUITING

Cincinnati, Ohio, 45229, United States
Indiana University/Riley Hospital for Children
RECRUITING

Indianapolis, Indiana, 46202, United States
Levine Children's Hospital at Carolinas
RECRUITING

Charlotte, North Carolina, 28203, United States
Lurie Children's Hospital of Chicago
RECRUITING

Chicago, Illinois, 60611, United States
Memorial Sloan Kettering Cancer Center
RECRUITING

New York, New York, 10065, United States
Oregon Health & Science University
RECRUITING

Portland, Oregon, 97239, United States
Phoenix Children's Hospital
RECRUITING

Phoenix, Arizona, 85016, United States
Primary Children's Hospital
RECRUITING

Salt Lake City, Utah, 84113, United States
Seattle Children's Hospital
RECRUITING

Seattle, Washington, 98105, United States
Sidney Kimmel Cancer Center at Johns Hopkins
RECRUITING

Baltimore, Maryland, 21231, United States
St. Jude Children's Research Hospital Memphis
RECRUITING

Memphis, Tennessee, 38105, United States
University of California San Francisco
RECRUITING

San Francisco, California, 94158, United States
University of Miami
RECRUITING

Miami, Florida, 33136, United States

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