Clinical Trial Finder

Inclusion Criteria:

• - Histologically confirmed malignancy at either original diagnosis or relapse, including the following: - Solid tumor, including primary CNS tumors.

• - Neurologic deficits in patients with CNS tumors must have been relatively stable for ≥ 1 week.

• - Patients with CNS tumors must be on stable or decreasing doses of dexamethasone for the past 7 days.

• - Histology requirement waived for intrinsic brain stem tumors.

• - Lymphoma.

• - Measurable or evaluable disease.

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

• - Patients with known bone marrow metastases are eligible for study but are not evaluable for hematologic toxicity.

• - Not known to be refractory to red blood cell or platelet transfusions.

• - Karnofsky performance score (PS) 60-100% (> 10 years of age) or Lansky PS 60-100% (≤ 10 years of age) - Absolute neutrophil count ≥ 1,000/mm³ - Platelet count ≥ 100,000/mm³ (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to study enrollment) - Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed) - Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age as follows: - No greater than 0.8 mg/dL (≤ 5 years of age) - No greater than 1.0 mg/dL (6 to 10 years of age) - No greater than 1.2 mg/dL (11 to 15 years of age) - No greater than 1.5 mg/dL (> 15 years of age) - Bilirubin ≤ 1.5 times upper limit of normal.

• - ALT ≤ 45 U/L.

• - Albumin ≥ 2 g/dL.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - No evidence of active graft-vs-host disease.

• - No uncontrolled infection.

• - Recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.

• - More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) - More than 1 week since prior growth factors, including those that support platelet or WBC number or function.

• - At least 1 week since prior biologic agents.

• - At least 2 weeks since prior local, palliative, small-port external-beam radiotherapy.

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

• - At least 6 weeks since other prior substantial bone marrow radiotherapy (i.e., skull, spine, pelvis, or ribs) - At least 3 months since prior stem cell transplantation or rescue without TBI.

• - No other concurrent investigational drugs.

• - No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy.

• - No concurrent enzyme-inducing anticonvulsants, including any of the following: - Phenytoin.

• - Phenobarbital.

• - Felbamate.

• - Primdone.

• - Oxcarbazepine.

• - Carbamazepine.

• - No concurrent agents that inhibit CYP3A4, including any of the following: - Itraconazole.

• - Ketoconazole.

- Voriconazole

PRIMARY OBJECTIVES:

• I. Determine the maximum tolerated dose and recommended phase II dose of ispinesib in pediatric patients with refractory solid tumors or lymphoma.

• II. Define and describe the toxicities of ispinesib in these patients.

• III. Characterize the pharmacokinetics of ispinesib in these patients.

SECONDARY OBJECTIVES:

• I. Define, preliminarily, the antitumor activity of ispinesib.

• II. Determine the relationship between CYP3A4 gene polymorphisms and pharmacokinetics in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study. Patients receive ispinesib IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ispinesib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients undergo blood and tumor sample collection periodically for pharmacokinetic and gene polymorphism correlative studies. After completion of study therapy, patients are followed for 30 days.

Arms

Experimental: Arm I

Patients receive ispinesib IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - ispinesib

Given IV

Other: - laboratory biomarker analysis

Correlative studies

Other: - pharmacological study

Correlative studies