Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, 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