ABT-751 in Treating Children With Neuroblastoma That Has Relapsed or Not Responded to Previous Treatment

Inclusion Criteria:

• Histologically or cytologically confirmed neuroblastoma meeting the following criteria:

  • Refractory or relapsed disease
  • No curative treatment option and no additional therapy proven to prolong survival with an acceptable quality of life is available
  • Evidence of disease progression (enlargement of existing measurable tumors or the appearance of new tumors) during prior treatment OR biopsy-proven viable neuroblastoma if stable disease but refractory to prior treatment

• Previously irradiated soft tissue or bony lesion must meet ≥ 1 of the following criteria:

  • Viable neuroblastoma determined by biopsy ≥ 6 weeks after radiation therapy
  • Growth in the lesion determined by CT scan or MRI

• Measurable or evaluable disease

  • Measurable disease is defined as ≥ 20 mm in ≥ 1 dimension by MRI, CT scan, or x-ray OR ≥ 10 mm in ≥ 1 dimension by spiral CT scan

  • Evaluable disease is defined as iodine I 123 metaiodobenzylguanidine (^123I MIBG)-positive lesion at ≥ 1 site

    • Must not have measurable disease by CT scan or MRI
  • No elevated urinary catecholamines and/or bone marrow evidence of tumor, without measurable or evaluable disease by imaging modalities (CT scan, MRI, or ^123I MIBG)
• Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age)
• Life expectancy ≥ 8 weeks
• Hemoglobin ≥ 7.5 g/dL (transfusions allowed)
• Absolute neutrophil count > 250/mm³
• Platelet count > 25,000/mm³ (without platelet transfusion support for ≥ 7 days)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT < 5 times ULN

• Creatinine normal for age and gender as follows: OR creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min

  • No greater than 0.4 mg/dL (≤ 5 months)
  • No greater than 0.5 mg/dL (6 months-11 months)
  • No greater than 0.6 mg/dL (1 year-23 months)
  • No greater than 0.8 mg/dL (2 years-5 years)
  • No greater than 1.0 mg/dL (6 years-9 years)
  • No greater than 1.2 mg/dL (10 years-12 years)
  • No greater than 1.4 mg/dL (13 years and over [female])
  • No greater than 1.5 mg/dL (13 years to 15 years [male])
  • No greater than 1.7 mg/dL (16 years and over [male])
• Shortening fraction ≥ 27% by echocardiogram
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 90 days after completion of study treatment
• Seizure disorder allowed if controlled and receiving anticonvulsants
• Neurologic toxicity from prior therapy or tumor involvement ≤ grade 2
• No evidence of active graft-vs-host disease
• No allergy to sulfa-containing medications
• No known HIV positivity
• No clinically significant unrelated systemic illness (e.g., serious infection) that would limit study compliance
• Concurrent filgrastim (G-CSF) allowed if medically indicated
• Recovered from all prior therapy
• No prior ABT-751
• More than 2 weeks since prior myelosuppressive chemotherapy
• More than 7 days since prior anticancer biologic agents (e.g., retinoids)
• More than 4 weeks since prior palliative radiation therapy (small port) or therapeutic ^123I MIBG
• More than 6 weeks since prior substantial radiation therapy (> 50% pelvis, craniospinal, or total-body radiation)

• More than 4 months since prior allogeneic stem cell transplantation (SCT) (2 months for autologous SCT) and recovered

  • Infusion of autologous peripheral blood mononuclear cells without high-dose chemotherapy or preparative regimen is not considered SCT
• More than 30 days since prior investigational drug therapy
• More than 30 days since prior immunotherapy (monoclonal antibody therapy or vaccine therapy)
• More than 1 week since prior growth factor treatment
• No other concurrent anticancer agents, including chemotherapy, immunomodulating agents, or biologic therapy (retinoids)
• No concurrent radiation therapy, including palliative radiation therapy
• No concurrent treatment for graft-vs-host disease
• No concurrent epoetin alfa, sargramostim (GM-CSF), or interleukin-11