OBJECTIVES:

Primary

• Determine the maximum tolerated dose and recommended phase II dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in pediatric patients with relapsed or refractory solid tumors or leukemia.
• Determine the toxic effects of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.

Secondary

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

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

Patients with solid tumors receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 60-120 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, up to 6 additional patients with leukemia receive 17-AAG at the MTD as above. If these 6 patients tolerate this regimen, another 6 leukemia patients receive 17-AAG IV over 60 minutes on days 1, 4, 8, 11, 15, and 18. Treatment repeats every 28 days for 17 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A maximum of 36 (3-24 with solid tumors and 12 with leukemia) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of solid tumor or leukemia with documented M3 marrow

  • Histologic confirmation of intrinsic brain stem tumors not required
• Relapsed or refractory disease
• No known curative therapy
• In patients with CNS tumors, neurologic deficits must be stable for at least the past week

PATIENT CHARACTERISTICS:

Age

• 1 to 21

Performance status

• Karnofsky 50-100% (>10 years of age)
• Lansky 50-100% (≤ 10 years of age)

Life expectancy

• Not specified

Hematopoietic

• For patients with solid tumors:

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

• For patients with leukemia:

  • Platelet count ≥ 20,000/mm^3 (may receive platelet transfusions)
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN
• Albumin ≥ 2 g/dL

Renal

• Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min OR

• Creatinine based on age as follows:

  • ≤ 0.8 mg/dL if ≤ 5 years of age
  • ≤ 1.0 mg/dL if > 5 years and ≤ 10 years of age
  • ≤ 1.2 mg/dL if > 10 years and ≤ 15 years of age
  • ≤ 1.5 mg/dL if > 15 years and ≤ 21 years of age

Other

• No uncontrolled infection
• No prior severe allergy to eggs
• No situation that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 7 days (or window for adverse effects has passed) since prior biologic therapy and recovered
• At least 7 days since prior hematopoietic growth factors
• At least 2 months since prior stem cell transplantation and no evidence of graft-vs-host disease
• No concurrent hematopoietic growth factors
• No concurrent biologic therapy
• No concurrent immunotherapy

Chemotherapy

• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent steroid therapy

Radiotherapy

• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 3 months since prior total body irradiation or craniospinal radiotherapy
• At least 3 months since prior radiotherapy to ≥ 50% of the pelvis
• At least 6 weeks since prior substantial bone marrow radiotherapy
• Recovered from prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• No other concurrent investigational drugs
• No other concurrent anticancer agents
• No concurrent phenytoin or phenobarbital
• No concurrent warfarin