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.