A Phase II Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, in Children With Relapsed or Refractory Neuroblastoma

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