A Phase 2 Study of the MEK Inhibitor Trametinib in Children With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

Inclusion Criteria
Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease
Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality
Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
Patients must not be known to be refractory to red blood cell or platelet transfusions
Exclusion Criteria
Patients who are pregnant or breast-feeding
Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment
Patients who are currently receiving another investigational drug
Patients who are currently receiving other anti-cancer agents
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
Any medications for treatment of left ventricular systolic dysfunction
Patients who are unable to swallow capsules or liquid
Patients who have an uncontrolled infection
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study
Patients with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months
Patients with a history of current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease(s) such as hypertension, diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes)