Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	1 to 21	NCI	COG-ADVL0316 ADVL0316, NCT00079404

Objectives

Primary

1. 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.
2. Determine the toxic effects of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.

Secondary

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

Entry 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

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

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/mm³
  • Platelet count ≥ 100,000/mm³ (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
• For patients with leukemia:
  • Platelet count ≥ 20,000/mm³ (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

Expected Enrollment

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

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.

Weigel BJ, Blaney SM, Reid JM, et al.: A phase I study of 17-allylaminogeldanamycin in relapsed/refractory pediatric patients with solid tumors: a Children's Oncology Group study. Clin Cancer Res 13 (6): 1789-93, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Brenda Weigel, MD, Protocol chair		Ph: 612-626-5501; 888-226-2376
Joseph Neglia, MD, MPH, Protocol co-chair		Ph: 612-626-2778; 888-226-2376 Email: jneglia@t.umn.edu

Registry Information
Official Title		A Phase I Study of 17-AAG in Relapsed/Refractory Pediatric Patients With Solid Tumors or Leukemia
Trial Start Date		2004-03-01
Registered in ClinicalTrials.gov		NCT00079404
Date Submitted to PDQ		2004-02-04
Information Last Verified		2005-04-05
NCI Grant/Contract Number		CA97452

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