Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children

Inclusion Criteria: 1. Patients must have either of the following: 1. Relapsed/refractory leukemia in 2nd or greater relapse or who have failed at least one re-induction attempt after relapse or for refractory disease. Patients must meet the WHO classification with ≥ 5% blasts in the bone marrow or must have definitive extramedullary disease (e.g. chloromas, skin lesions). Patients may have asymptomatic CNS 1 or CNS 2 disease, but not CNS 3 or symptomatic CNS disease. OR 2. Relapsed/refractory non-CNS solid tumor that has not responded or has relapsed and for which no standard treatment is available. Patients may not have primary CNS tumors or CNS metastases. Lymphoma patients are permitted. Patients do not need to have measurable disease. 2. Age 6 months - 29.99 years at enrollment 3. Life expectancy ≥ 3 months 4. Lansky or Karnofsky ≥50 5. Prior therapy 1. Patient must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, radiotherapy, or surgery prior to study entry. 2. Myelosuppressive therapy- At least 14 days must have elapsed since the administration of previous therapy. Six weeks must have elapsed from the administration of nitrosureas or mitomycin C. For patients with ALL on maintenance therapy, they may be eligible if 7 days have elapsed and they are recovered from the toxic effects of the chemotherapy. This restriction does not include intrathecal chemotherapy, which is permitted. 3. Biologic agents- At least 14 days must have elapsed since the completion of therapy with a biologic agent such as a monoclonal antibody. Seven days must have elapsed since the last dose of retinoids 4. Radiation therapy - At least 14 days must have elapsed for local XRT. At least 90 days must have elapsed if prior radiation to ≥50% of the pelvis, the spine, or other substantial bone marrow radiation including TBI. 5. Hematopoietic growth factors- At least 7 days must have elapsed since the last dose of G-CSF or GM-CSF. At least 14 days must have elapsed since last dose of pegfilgrastim (Neulasta®). 6. Patient must be ≥ 3 months from hematopoietic stem cell transplant, must not have active GVHD, and must be off all immunosuppression 7. Organ function: 1. Either a serum creatinine ≤ ULN for age, or calculated or measured GFR ≥ 70 mL/min/1.73 m2 2. Total bilirubin ≤ 1.5 x ULN for age, direct bilirubin ≤ ULN for age 3. AST and ALT ≤ 3 x ULN for age unless elevation can be clearly attributed to liver leukemia or metastases 4. ECHO shortening fraction ≥ 27% 5. Pulse Oximetry measurement ≥ 95% saturation without supplemental oxygen 8. Bone marrow function: 1. Hgb ≥10 g/dL - can be transfused 2. Plts ≥ 75,000 - cannot be transfused (must be ≥ 7 days from last plt transfusion) 3. ANC ≥ 750 - cannot be transfused (must be ≥ 72 hours from last neutrophil infusion) However, the plt and ANC requirements can be waived if low counts thought to be secondary to leukemia or tumor bone marrow infiltration 9. Reproductive function: 1. Female patients of childbearing potential must have a negative serum pregnancy test confirmed within 7 days prior to enrollment 2. Female patients with infants must agree not to breastfeed their infants while on the study 3. 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 3 months after study treatment 10. Written informed consent Exclusion Criteria: 1. Prior treatment with carfilzomib 2. Known allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib). 3. Down syndrome 4. Fanconi Anemia or other underlying bone marrow failure syndrome 5. Pregnant or lactating females 6. Known history of Hepatitis B or C or HIV 7. Patient with any significant concurrent illness 8. Patient with uncontrolled systemic fungal, bacterial, viral or other infection with ongoing signs/symptoms despite appropriate treatment 9. Patient with illness, psychiatric disorder or social issue that could compromise patient safety or compliance with the protocol treatment or procedures, or interfere with the consent, study participation, follow-up, or interpretation of study results.