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New treatment option for Leukemia, Juvenile Myelomonocytic
Official title A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia
ClinicalTrials.gov ID: NCT05849662
What this study is testing
What is Trametinib?
Trametinib is an investigational medicine, given as an once-daily, being studied as a potential treatment for leukemia, juvenile myelomonocytic.
Also referred to as GSK1120212B, TMT212-NXA.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 1 to 21
You may be able to join if
- Patients must be ≥ 1 month and ≤21 years of age at enrollment. Diagnosis Patients must meet the 2022 International Consensus Classification criteria...
- Peripheral blood monocyte count ≥ 1 × 109/L\
- Splenomegaly†
- Blast percentage in PB and BM \< 20%
- Absence of BCR::ABL1
You likely can't join 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...
- 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...
- Patients cannot have a clinical or molecular diagnosis of Noonan syndrome. Note: patients with either neurofibromatosis type 1 or Casitas B-lineage...
- Patient cannot have had prior use of hematopoietic growth factors, biologics (anti-neoplastic agent), or XRT.
See the full eligibility criteria
- 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...
- 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...
- 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...
- 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). 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.
- 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...
- 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...
- 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...
- 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.
The study team makes the final eligibility decision.
Where it's taking place
- Phoenix, Arizona, United States
- Los Angeles, California, United States
- San Francisco, California, United States
- Denver, Colorado, United States
- Washington D.C., District of Columbia, United States
- Miami, Florida, United States
- Atlanta, Georgia, United States
- Chicago, Illinois, United States
- Indianapolis, Indiana, United States
- Baltimore, Maryland, United States
- Ann Arbor, Michigan, United States
- Kansas City, Missouri, United States
- New York, New York, United States
- Cincinnati, Ohio, United States
- Portland, Oregon, United States
- Philadelphia, Pennsylvania, United States
- Memphis, Tennessee, United States
- Salt Lake City, Utah, United States
- Seattle, Washington, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 1 month to 21 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Phoenix, Arizona, United States; Los Angeles, California, United States; San Francisco, California, United States; Denver, Colorado, United States; Washington D.C., District of Columbia, United States; Miami, Florida, United States and 13 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.