RATIONALE: Drugs used in chemotherapy, such as 17-DMAG, work in different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of 17-DMAG in treating patients who have metastatic or unresectable solid tumors or lymphomas.

Condition	Treatment or Intervention	Phase
adult solid tumor Leukemia Lymphoma	Drug: 17-dimethylaminoethylamino-17-demethoxygeldanamycin  Procedure: chemotherapy	Phase I

OBJECTIVES: Primary

• Determine the maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with metastatic or unresectable solid tumors or lymphomas.
• Determine the safety and toxicity of this drug in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
• Determine the recommended phase II dose of this drug for future studies.

Secondary

• 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 hour 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.

PROJECTED ACCRUAL: A total of 3-60 patients will be accrued for this study within 14-18 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

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

Renal

• Creatinine ≤ 1.25 times ULN OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• 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

PRIOR CONCURRENT THERAPY: Biologic therapy

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

Chemotherapy

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

Endocrine therapy

• Concurrent hormonal therapy allowed

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies
• No other concurrent investigational agents

Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Ohio
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting

Study chairs or principal investigators

Ramesh K. Ramanathan, MD,  Study Chair,  University of Pittsburgh Cancer Institute   

Study ID Numbers:  CDR0000378189; PCI-03-153; NCI-6548; PCI-IRB-0404083
Record last reviewed:  July 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089271
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-22