A Phase I Study of Obatoclax (Pan Anti-Apoptotic BCL-2 Family Small Molecule Inhibitor), in Combination With Vincristine/Doxorubicin/Dexrazoxane, in Children With Relapsed/Refractory Solid Tumors or Leukemia

Inclusion Criteria:

- Diagnosis of 1 of the following:

- Histologically confirmed refractory or relapsed solid tumor or lymphoma (stratum
1)

- Measurable or evaluable disease

- No primary CNS tumors

- No known CNS metastases

- Recurrent or refractory mixed-lineage leukemia (MLL) leukemia (stratum 2)

- More than 25% blasts on bone marrow aspirate

- No symptomatic CNS leukemia, CNS chloromas, or leptomeningeal leukemic
involvement

- Recurrent or refractory non-MLL leukemia (stratum 3)

- Acute lymphoblastic leukemia, acute myeloid leukemia, or chronic myeloid
leukemia in blast crisis

- More than 25% blasts on bone marrow aspirate

- No symptomatic CNS leukemia, CNS chloromas, or leptomeningeal leukemic
involvement

- No known curative therapy or therapy proven to prolong survival with an acceptable
quality of life

- Karnofsky performance status 50-100% (> 16 years of age)

- Lansky performance status 50-100% (≤ 16 years of age)

- ANC ≥ 1,000/mm^3 (stratum 1)

- Platelet count ≥ 100,000/mm^3 (transfusion independent defined as ≥ 7 days since
prior transfusion)(stratum 1)

- Platelet count ≥ 20,000/mm^3 (may receive platelet transfusion) (stratum 2 and 3)

- Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusion)

- Creatinine clearance OR radioisotope GFR ≥ 70 mL/min OR serum creatinine based on
age/gender as follows:

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

- Bilirubin (sum of conjugated and unconjugated) ≤ 1.5 times upper limit of normal

- ALT ≤ 110 U/L

- Serum albumin ≥ 2 g/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Adequate cardiac function defined as 1 of the following:

- Shortening fraction ≥ 27% by echocardiogram

- Ejection fraction ≥ 50% by gated radionuclide study

- Central nervous system function defined as:

- Stable neurological examination ≥ 2 weeks prior to study

- No known unresolved neurological toxicities > grade 2

- No uncontrolled infection

- Must be able to comply with the safety-monitoring requirements of the study according
to the primary investigator's opinion

- No prior total lifetime cumulative anthracycline dose > 750 mg/m^2 (25 mg/kg if
patient < 1 year) of doxorubicin hydrochloride or equivalent (e.g., daunorubicin
hydrochloride, idarubicin, or mitoxantrone hydrochloride)

- Recovered from all prior chemotherapy, immunotherapy, or radiotherapy

- At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)

- At least 24 hours since prior hydroxyurea

- At least 7 days since prior hematopoietic growth factor

- At least 7 days since prior biologic therapy

- Time must be extended for other biological agents known to have adverse events
beyond 7 days, at the discretion of the primary investigator

- At least 6 weeks since prior immunotherapy (e.g., tumor vaccine)

- At least 3 half-lives since prior monoclonal antibody therapy

- Prior radiotherapy allowed according to the following criteria:

- At least 2 weeks since prior palliative radiotherapy (small port)

- At least 6 months since prior total-body irradiation (TBI), craniospinal
radiotherapy, or ≥ 50% radiation of the pelvis

- At least 6 weeks since other prior substantial bone marrow radiation

- At least 3 months since prior stem cell transplantation or rescue without TBI and no
evidence of active graft-vs-host disease

- More than 7 days since prior growth factor that supports platelet or white cell
number or function

- Stable or decreasing dose of corticosteroid in the past 7 days

- No concurrent investigational drugs

- No other concurrent anticancer agents (including chemotherapy, radiotherapy,
immunotherapy, or biologic therapy) except for hydroxyurea

- Patients with leukemia may receive concurrent anticancer agents (methotrexate,
hydrocortisone, cytarabine) intrathecally, if necessary

- No concurrent anticonvulsants