RATIONALE: Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, 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-N-allylamino-17-demethoxygeldanamycin in treating young patients who have relapsed or refractory solid tumors or leukemia.

Condition	Treatment or Intervention	Phase
unspecified childhood solid tumor, protocol specific recurrent childhood acute lymphoblastic leukemia recurrent childhood acute myeloid leukemia secondary acute myeloid leukemia acute undifferentiated leukemia	Drug: 17-N-allylamino-17-demethoxygeldanamycin  Procedure: chemotherapy	Phase I

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 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.

Ages Eligible for Study:  1 Year   -   21 Years,  Genders Eligible for Study:  Both

Criteria

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 administration of medications known to be metabolized by the CYP4503A isoenzyme

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States; Recruiting
      Lucile Packard Children's Hospital at Stanford University Medical Center, Palo Alto,  California,  94304,  United States; Recruiting
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States; Recruiting
Georgia
      MBCCOP-Medical College of Georgia Cancer Center, Augusta,  Georgia,  30912-4000,  United States; Recruiting
Indiana
      Riley Children Cancer Center at Riley Hospital for Children, Indianapolis,  Indiana,  46202-5225,  United States; Recruiting
Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      SUNY Downstate Medical Center, Brooklyn,  New York,  11203,  United States; Recruiting
Ohio
      Cincinnati Children's Hospital Medical Center, Cincinnati,  Ohio,  45229-3039,  United States; Recruiting
Oregon
      Doernbecher Children's Hospital at Oregon Health & Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213-2583,  United States; Recruiting
Tennessee
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States; Recruiting
Texas
      MBCCOP - South Texas Pediatrics, San Antonio,  Texas,  78229-3900,  United States; Recruiting
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-9063,  United States; Recruiting
      Texas Children's Cancer Center, Houston,  Texas,  77030-2399,  United States; Recruiting
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States; Recruiting
Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada; Recruiting
Canada, Quebec
      Hopital Sainte Justine, Montreal,  Quebec,  H3T 1C5,  Canada; Recruiting

Study chairs or principal investigators

Brenda Weigel, MD,  Study Chair,  University of Minnesota Cancer Center   
Joseph P. Neglia, MD, MPH,  University of Minnesota Cancer Center   

Study ID Numbers:  CDR0000355714; COG-ADVL0316
Record last reviewed:  March 2004
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00079404
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-29