Study of Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children With Relapsed or Refractory Solid Tumors and Leukemias

Inclusion Criteria:

- Participants must have either of the following:

- 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

- 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.

- Age 6 months - 29.99 years at enrollment

- Life expectancy >/= 3 months

- Lansky or Karnofsky >/= 50

- Prior therapy

- Participant must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, radiotherapy, or surgery prior to study entry.

- Myelosuppressive therapy - At least 14 days must have elapsed since the administration
of previous therapy. Six weeks must have elapsed from the administration of
nitrosoureas or mitomycin C. For participants 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. Hydroxyurea is permitted but must be discontinued >/= 24 hours prior to
start of protocol therapy.

- 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

- 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.

- 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).

- Participants must be >/= 3 months from hematopoietic stem cell transplant, must
not have active GVHD, and must be off all immunosuppression

Laboratory

- Organ function:

- Either a serum creatinine /= 70
mL/min/1.73 m2

- Total bilirubin
- AST and ALT liver leukemia or metastases

- ECHO shortening fraction >/= 27%

- Pulse oximetry measurement >/= 95% saturation without supplemental oxygen

- Bone marrow function

- Hgb >/= 10 g/dL - can be transfused

- Plts >/= 75,000 - cannot be transfused (must be >/= 7 days from last plt
transfusion)

- ANC >/= 750 - cannot be transfused (must be >/= 72 hours from last neutrophil
infusion) However, the ply and ANC requirements can be waived if low counts
through to be secondary to leukemia or tumor bone marrow infiltration

Ethical/Other

- Reproductive function

- Female participants of childbearing potential must have a negative serum
pregnancy test confirmed within 7 days prior to enrollment

- Female participants with infants must agree not to breastfeed their infants while
on the study

- Male and female participants 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

- Written informed consent

Exclusion Criteria:

- Prior treatment with carfilzomib

- Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)

- Down syndrome

- Fanconi Anemia or other underlying bone marrow failure syndrome

- Pregnant or lactating females

- Known history of Hepatitis B or C or HIV

- Participant with any significant concurrent illness

- Participant with uncontrolled systemic fungal, bacterial, viral or other infection
with ongoing signs/symptoms despite appropriate treatment

- Participant with illness, psychiatric disorder or social issue that could compromise
participant safety or compliance with the protocol treatment or procedures, interfere
with the consent, study participation, follow-up, or interpretation of study results