Mirdametinib in Histiocytic Disorders

Exclusion Criteria

• •1. Prior therapy with stipulations as described:
• •* Myelosuppressive Chemotherapy: Must not have received any cytotoxic chemotherapy which impacts the growth and development of cells in the bone marrow within 14 days of enrollment onto this study (i.e. cytarabine, cladribine, clofarabine, mercaptopurine, methotrexate, vinblastine)
• •* MEK Inhibitors: Must not have received a MEK inhibitor within 30 days (or 5 half-lives, whichever is longer) of enrollment, NOR have had disease progression on MEK inhibitor
• •* Radiation: Must not have received radiation within 14 days of study enrollment or have received radiation to the orbit at any time
• •2. Risk factors for retinal vein occlusion (RVO) are listed. Exclusion should be considered by clinical discretion if they have any of the following risk factors for RVO at screening:
• •* Intraocular pressure (IOP) \> 21 mmHg; if IOP is unable to be obtained (eg age, cooperation, tolerability), ophthalmologist's exam findings and overall assessment will be utilized. If in the ophthalmologist's assessment there are no signs of raised IOP, the subject will be considered eligible for this parameter
• •* Glaucoma or any significant abnormality (≥ grade 2) on ophthalmologic exam that is uncontrolled with intervention
• •* Serum cholesterol \> 300 mg/dL
• •* Serum triglycerides \> 300 mg/dL
• •* Hyperglycemia (either fasting blood glucose \> 125 mg/dL OR random blood glucose \> 200 mg/dL)
• •* Uncontrolled hypertension (participants ≤ 12 years of age with a blood pressure ≥ 95th percentile for age + 12 mmHg; participants ≥ 13 years of age with a blood pressure ≥ 140/90 mm Hg) unresolved on repeat measurement
• •3. LVEF \< 55% at screening OR history of clinically significant cardiac disease, unless deemed to be the direct result of disease
• •4. Subjects who are pregnant or breastfeeding, or are at risk of pregnancy or fathering a baby and are unable to use acceptable methods of birth control during the length of the study