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

PRIMARY OBJECTIVES:

I. Compare the time to disease progression in children with refractory or relapsed
neuroblastoma treated with ABT-751 vs historical controls.

SECONDARY OBJECTIVES:

I. Determine the objective response rate in patients with measurable disease treatment with
this drug.

II. Determine whether ABT-751 improves quality of life of these patients. III. Determine the
toxicity of ABT-751. IV. Determine the pharmacokinetic profile of ABT-751 in these patients.

OUTLINE:

Patients receive oral ABT-751 once daily on days 1-7. Treatment repeats every 21 days for 52
courses in the absence of disease progression or unacceptable toxicity.

Blood is collected periodically during course 1 for pharmacokinetic studies. Quality of life
is assessed at baseline and prior to each course of treatment.

After completion of study treatment, patients are followed up for up to 5.1 years.

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