Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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 who have an uncontrolled infection are not eligible
* 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 with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months 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 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
* 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