Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

Prior treatment

• Patients who are pregnant or breast-feeding are not eligible for this study as there is yet no available information regarding human fetal or teratogenic toxicities; negative pregnancy tests must be obtained in girls who are post-menarchal; patients of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; women of childbearing potential should be advised to use effective contraception for 4 months after the last dose of trametinib; trametinib may also potentially be secreted in milk and therefore breastfeeding women are excluded; female patients should not breastfeed during treatment with trametinib, and for 4 months following the last dose; male patients must use a condom during intercourse and agree not to father a child during therapy and for 4 months following discontinuation of trametinib to avoid unnecessary exposure of trametinib to the fetus
• Concomitant Medications
  • Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
  • Note: hydrocortisone used as a pre-medication to prevent transfusion related reactions is not considered a concomitant corticosteroid
  • Investigational drugs: patients who are currently receiving another investigational drug are not eligible
  • Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible (except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
  • Anti-graft versus host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
  • Cardiac medications: any medications for treatment of left ventricular systolic dysfunction
• Patients with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months are not eligible

Other illness

• Patients who have an uncontrolled infection are not eligible
• Patients with a history of or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
• Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension
• Patients with a history of allergic reaction attributed to compounds of similar chemical or biologic composition to the MEK inhibitor, trametinib are not eligible
• Patients with a clinical diagnosis of Noonan syndrome are not eligible; Note: patients with Casitas B-lineage lymphoma (CBL) syndrome, also known as Noonan-like syndrome, are eligible to enroll

Age

• Patients with uncontrolled systemic disease(s) such as hypertension or diabetes mellitus are not eligible; blood pressure must be =\< the 95th percentile for age, height, and gender

Other

• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

• Patients must be \>= 1 month and \< 22 years of age at the time of study entry
• Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease; the diagnosis is made based on the following criteria
  • JMML category 1 (all of the following): the diagnostic criteria must include all features in category 1 and EITHER (i) one of the features in category 2 OR (ii) two features from category 3 to make the diagnosis
  • Splenomegaly
  • \> 1000 (1 x 10\^9/uL) circulating monocytes
  • \< 20% blasts in the bone marrow or peripheral blood
  • Absence of the t(9;22) or BCR/ABL fusion gene
  • JMML category 2 (at least one of the following if at least two category 3 criteria are not present):
  • Somatic mutation in RAS or PTPN11
  • Clinical diagnosis of NF1 or NF1 gene mutation
  • Homozygous mutation in CBL
  • Monosomy 7
  • JMML category 3 (at least two of the following if no category 2 criteria are met):
  • Circulating myeloid precursors
  • White blood cell count, \> 10 000 (10 x 10\^9/ uL)
  • Increased hemoglobin F for age
  • Clonal cytogenetic abnormality
  • GM-CSF hypersensitivity
• Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to AML at any point with more than 20% blasts are not eligible for this trial
• Patients must have a Lansky or Karnofsky performance status score of \>= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
  • Myelosuppressive chemotherapy: patients must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
  • Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy
  • Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
  • Monoclonal antibodies:
  • At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines
  • At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
  • Radiotherapy:
  • \>= 2 weeks must have elapsed since local palliative external radiation therapy (XRT) (small port)
  • \>= 6 months must have elapsed if prior craniospinal XRT was received, if \>= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received
  • \>= 4 weeks must have elapsed if other substantial bone marrow irradiation was given
  • Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and \>= 3 months must have elapsed since transplant; \>= 4 weeks must have elapsed since any donor lymphocyte infusion
• Patients must not be known to be refractory to red blood cell or platelet transfusions
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
  • Age: Maximum serum creatinine (mg/dL)
  • 1 month to \< 6 months: 0.4 (male) 0.4 (female)
  • 6 months to \< 1 year: 0.5 (male) 0.5 (female)
  • 1 to \< 2 years: 0.6 (male) 0.6 (female)
  • 2 to \< 6 years: 0.8 (male) 0.8 (female)
  • 6 to \< 10 years: 1 (male) 1 (female)
  • 10 to \< 13 years: 1.2 (male) 1.2 (female)
  • 13 to \< 16 years: 1.5 (male) 1.4 (female)
  • \>= 16 years: 1.7 (male) 1.4 (female)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 3 x ULN (=\< 135 U/L) (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin \>= 2 g/dL (within 7 days prior to enrollment)
• Shortening fraction of \>= 27% by echocardiogram OR ejection fraction of \>= 50% by multi-gated acquisition (MUGA)
• Corrected QT (by Bazett's formula \[QTcB\]) interval \< 450 msecs
• Patients must be able to swallow tablets or liquid; use of a nasogastric or gastrostomy (G) tube is also allowed