RATIONALE: AT7519M may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of AT7519M in treating patients with advanced or metastatic solid tumors or refractory non-Hodgkin's lymphoma.

OBJECTIVES:

Primary

• Determine the recommended phase II dose of AT7519M in patients with advanced or metastatic solid tumors or refractory non-Hodgkin's lymphoma.
• Determine the safety, tolerability, toxicity profile, and dose-limiting toxicities of this drug in these patients.
• Determine the pharmacokinetic profile of this drug in these patients.
• Correlate the toxicity profile with pharmacokinetics of this drug in these patients.

Secondary

• Assess, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive AT7519M IV over 1-3 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AT7519M 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 during course 1. Once the MTD has been determined, up to 8 additional patients are treated at the MTD.

Patients undergo blood collection periodically for pharmacokinetic studies. Patients treated at the MTD also undergo tumor tissue biopsies or aspirates and blood collection periodically for additional pharmacodynamic and correlative biomarker studies.

After completion of study therapy, patients are followed at 4 weeks. Patients with complete response, partial response, or stable disease are followed every 3 months thereafter until relapse.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of 1 of the following:

  • Advanced and/or metastatic solid tumor

    • No more than 3 prior regimens for metastatic disease

  • Refractory non-Hodgkin's lymphoma

• Clinically or radiologically documented disease

  • Patients whose only evidence of disease is tumor marker elevation are not eligible

• No untreated brain or meningeal metastases

  • Patients with radiologic or clinical evidence of stable, treated brain metastases are eligible provided they are asymptomatic AND have no requirement for corticosteroids

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Absolute granulocyte count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine ≤ 1.25 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min

• Bilirubin normal

• ALT and AST ≤ 2 times ULN (5 times ULN if patient has documented liver metastases)

• Potassium normal

• Calcium normal

• Creatine kinase (CK or CPK) ≤ 2 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction, including any of the following:

  • Significant cardiac event (including symptomatic heart failure or angina) within the past 3 months or any cardiac disease that, in the opinion of the investigator, increases the risk for ventricular arrhythmia
  • Any history of ventricular arrhythmia, which was symptomatic or required treatment (CTC grade 3), including multifocal PVCs, bigeminy, trigeminy, or ventricular tachycardia
  • Uncontrolled hypertension
  • Previous history of QT prolongation with other medication
  • Congenital long QT syndrome
  • QT and QTc, with Bazett's correction, unmeasurable or ≥ 460 msec on screening ECG
  • LVEF < 45 % by MUGA for patients with significant cardiac history (i.e., myocardial infarction, severe hypertension, or arrhythmia) or prior doxorubicin (> 450 mg/m²)

• No active or uncontrolled infections

• No serious illness or medical condition that would preclude study compliance

• No peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 21 days since prior cytotoxic chemotherapy and recovered (solid tumors)

• At least 21 days since prior palliative radiotherapy and recovered

  • Exceptions may be made for low-dose, nonmyelosuppressive radiotherapy

• Prior hormonal, immunologic, biologic, or signal transduction inhibitor therapy allowed

• At least 14 days since prior major surgery and recovered (no nonhealing wounds)

• At least 4 weeks since prior steroids

• No other concurrent medications which affect QT/QTc and cannot be discontinued

• No other concurrent experimental drugs or anticancer therapy