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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079404
First received: March 8, 2004
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin in treating young patients with relapsed or refractory solid tumors or leukemia. 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.


Condition Intervention Phase
Acute Undifferentiated Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: tanespimycin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of 17-AAG in Relapsed/Refractory Pediatric Patients With Solid Tumors or Leukemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD defined as the maximum dose at which fewer than one-third of patients experience DLT [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: March 2004
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: tanespimycin
Given IV
Other Name: 17-AAG

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and recommended phase II dose of 17-AAG administered as a 60 or 120-minute intravenous infusion on days 1, 4, 8, and 11, of a 21-day course, to children with refractory solid tumors or relapsed leukemia.

II. To define and describe the toxicities of 17-AAG administered on this schedule.

III. To characterize the pharmacokinetics of 17-AAG in children with refractory cancer.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of 17-AAG within the confines of a phase I study.

II. To assess the biologic activity of 17-AAG. III. To examine the role of CYP3A5 polymorphisms in the pharmacologic and clinical phenotypes observed following administration of 17-AAG to children, within the confines of a phase 1 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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Performance status - Karnofsky 50-100% (>10 years of age)
  • Performance status - Lansky 50-100% (≤ 10 years of age)
  • 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)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 2.5 times ULN
  • Albumin ≥ 2 g/dL
  • Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min
  • 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
  • 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
  • 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
  • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
  • No other concurrent chemotherapy
  • No concurrent steroid therapy
  • 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
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents
  • No concurrent phenytoin or phenobarbital
  • No concurrent warfarin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079404

Locations
United States, California
COG Phase I Consortium
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Brenda Weigel COG Phase I Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079404     History of Changes
Other Study ID Numbers: NCI-2012-01811, ADVL0316, CDR0000355714, COG-ADVL0316, U01CA097452
Study First Received: March 8, 2004
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 26, 2014