This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic or unresectable solid tumors or lymphomas. Drugs used in chemotherapy, such as 17-DMAG, work in different ways to stop cancer cells from dividing so they stop growing or die

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with metastatic or unresectable solid tumors or lymphomas.

II. Determine the safety and toxicity of this drug in these patients. III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.

IV. Determine the recommended phase II dose of this drug for future studies.

SECONDARY OBJECTIVES:

I. Determine tumor response in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1-6 hours on days 1-3 or 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-2 patients receive accelerated escalating doses of 17-DMAG until at least 1 of 2 patients experience dose-limiting toxicity (DLT). Cohorts are then expanded to 3-6 patients who receive escalating doses (in a standard manner) of 17-DMAG 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 DLT.

Patients are followed at 4 weeks.

Inclusion Criteria:

• Histologically confirmed solid tumor or lymphoma

  • Metastatic or unresectable disease

• Standard curative or palliative measures do not exist or are no longer effective

• No known brain metastases

• Performance status - ECOG 0-2

• Performance status - Karnofsky 60-100%

• More than 12 weeks

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9.0 g/dL

• ALT and AST ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin ≤ normal

• Creatinine ≤ 1.25 times ULN

• Creatinine clearance ≥ 60 mL/min

• QTc < 450 msec for male patients (470 msec for female patients)

• LVEF > 40% by MUGA

• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)

• No myocardial infarction or active ischemic heart disease within the past year

• No New York Heart Association class III or IV congestive heart failure

• No poorly controlled angina

• No uncontrolled dysrhythmia requiring medication

• No left bundle branch block

• No history of congenital long QT syndrome

• No other significant cardiac disease

• Pulse oximetry at rest or on exercise > 88%

• No symptomatic pulmonary disease (e.g., chronic obstructive or restrictive pulmonary disease, etc.) or any of the following are allowed:

  • Pulmonary disease requiring medication
  • History of dyspnea, dyspnea on exertion, or paroxysmal nocturnal dyspnea
  • Patients meeting the Medicare criteria for home oxygen or are on oxygen

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double barrier contraception 1 week before, during, and for at least 2 weeks after study participation

• No uncontrolled illness

• No active or ongoing infection

• No history of allergic reaction attributed to compounds of similar chemical or biological composition to 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG)

• No psychiatric illness or social situation that would preclude study compliance

• No concurrent routine colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• Concurrent hormonal therapy allowed

• At least 4 weeks since prior radiotherapy and recovered

• No prior radiation that included the heart in the field (e.g., mantle)

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent anticancer agents or therapies

• No concurrent medication that would prolong the QTc interval

• No other concurrent investigational agents