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Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00093821
First received: October 6, 2004
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

This phase I trial is studying the side effects and best dose of tanespimycin in treating young patients with recurrent or refractory leukemia or selected solid tumors. Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop cancer cells from dividing so they stop growing or die.


Condition Intervention Phase
Childhood Chronic Myelogenous Leukemia
Childhood Desmoplastic Small Round Cell Tumor
Disseminated Neuroblastoma
Metastatic Childhood Soft Tissue Sarcoma
Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Metastatic Osteosarcoma
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Neuroblastoma
Recurrent Osteosarcoma
Drug: tanespimycin
Other: pharmacological study
Other: laboratory biomarker analysis
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 Multicenter Phase I Trial of 17-N-allylamino-17-demethoxy Geldanamycin (17-AAG, NSC #330507) in Patients With Recurrent/Refractory Pediatric Solid Tumors (Ewing's Sarcoma, Desmoplastic Small Round Cell Tumor, Osteosarcoma, Neuroblastoma, and Rhabdomyosarcoma) and Leukemia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD, defined as the highest dose level with an observed incidence of DLT in no more than 1 out of 6 patients treated at a particular dose level [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in Hsp90 client protein levels in relation to dose of tanespimycin [ Time Frame: Baseline to 21 days ] [ Designated as safety issue: No ]

Enrollment: 70
Study Start Date: September 2004
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tanespimycin)

Patients receive tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11 (for patients with solid tumors) OR days 1, 4, 8, 11, 15, and 18 (for patients with leukemia). Courses for all patients repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tanespimycin until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 15 patients are treated at the MTD.

Drug: tanespimycin
Given IV
Other Name: 17-AAG
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the dose-limiting toxicity and maximum tolerated dose (MTD) of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in pediatric patients with recurrent or refractory leukemia or selected solid tumors.

II. Determine the levels of key proteins known to influence cancer cell survival and proliferation in patients treated with this drug at the MTD.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of this drug in these patients. II. Evaluate effects of genetic polymorphisms known to alter the activity of enzymes involved in the metabolism of this drug.

III. Correlate the alteration of fludeoxyglucose F18 accumulation with tumor response in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to diagnosis (leukemia vs solid tumor).

Patients receive tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11 (for patients with solid tumors) OR days 1, 4, 8, 11, 15, and 18 (for patients with leukemia). Courses for all patients repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tanespimycin 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 dose-limiting toxicity. At least 15 patients are treated at the MTD.

Patients are followed for 30 days.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed diagnosis of 1 of the following malignancies:

    • Leukemia

      • Lymphoid, myeloid, or mixed lineage
      • Relapsed (in second or greater relapse) or refractory disease, confirmed by 1 of the following:

        • Bone marrow relapse, defined as either M3 bone marrow (> 25% blasts in the bone marrow aspirate) OR M2 bone marrow (5-25% blasts in the bone marrow aspirate) at any time after complete remission is attained
        • CNS relapse, defined as at least 5 WBC/mL by cytospin of any cerebrospinal fluid (CSF) specimen OR less than 5 WBC/mL by cytospin of 2 consecutive CSF specimens obtained >= 4 weeks apart and having definitive confirmation that blasts are derived from the original leukemic clone by molecular cytogenetics, multiparameter flow cytometry, or immunostaining of >= 2 antigens
      • Patients with underlying chronic myeloid leukemia must have > 25% blasts in the bone marrow aspirate
      • Patients with M3 bone marrow AND extramedullary sites of disease, other than leptomeningeal disease, are eligible
    • Solid tumor

      • One of the following tumor types:

        • Neuroblastoma
        • Ewing's sarcoma
        • Osteosarcoma
        • Desmoplastic small round cell tumor
        • Rhabdomyosarcoma
      • Progressed after prior standard therapy OR no effective standard therapy exists
      • Measurable or nonmeasurable disease
  • No known brain metastases
  • No active leptomeningeal leukemia, defined by the following criteria:

    • WBC > 5/mm^3 in cerebrospinal fluid (CSF)
    • Unequivocal confirmation of leukemic blasts in CSF by cell morphology
  • No symptomatic CNS disease (e.g., cranial nerve abnormalities) without cytologic abnormality in CSF
  • Performance status - Karnofsky 70-100% (for patients > 10 years of age)
  • Performance status - Lansky 70-100% (for patients =< 10 years of age)
  • More than 8 weeks
  • Absolute neutrophil count >= 750/mm^3
  • Platelet count >= 75,000/mm^3 (transfusion independent)
  • Hemoglobin >= 8.5 g/dL (transfusion allowed)
  • Bilirubin < 1.5 mg/dL
  • ALT and AST =< 2.5 times upper limit of normal (ULN)
  • INR =< 1.5 times ULN
  • Albumin > 2.0 g/dL
  • Creatinine =< 1.5 times ULN for age
  • Creatinine clearance or radioisotope glomerular filtration rate > 60 mL/min
  • Ejection fraction >= 50%
  • Shortening fraction >= 28%
  • QTc < 450 msec for men (470 msec for women)

    • No congenital long QT syndrome
  • LVEF > 40% by MUGA
  • No symptomatic congestive heart failure
  • No cardiac arrhythmia
  • No New York Heart Association class III or IV heart failure
  • No myocardial infarction within the past year
  • No uncontrolled dysrhythmias
  • No poorly controlled angina
  • More than 12 months since active ischemic heart disease
  • No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation >= 3 beats in a row)
  • No left bundle branch block
  • No other significant cardiac disease
  • No pulmonary fibrosis by radiography
  • No ongoing or active bacterial or fungal infection
  • No other uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance
  • No history of serious allergic reaction attributed to eggs or dimethyl sulfoxide
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Recovered from all immunotherapy
  • At least 6 months since prior allogeneic stem cell transplantation
  • At least 3 months since prior autologous stem cell transplantation
  • At least 2 weeks since prior biologic agents (e.g., monoclonal antibodies)
  • At least 1 week since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
  • Recovered from all prior chemotherapy
  • At least 2 weeks since prior chemotherapy (for patients with leukemia only)
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) (for patients with solid tumors)
  • No prior oxaliplatin
  • No concurrent corticosteroids except for the treatment of adrenal crises in patients with suppressed hypothalamic-pituitary-adrenal axis response OR for treatment of allergic reactions to medications or blood products
  • Recovered from all prior radiotherapy
  • At least 6 months since prior radiotherapy to >= 50% of the pelvis
  • At least 6 months since prior radiotherapy to substantial bone marrow, including total body irradiation
  • At least 4 weeks since prior local (small port) radiotherapy
  • No prior radiotherapy to the heart
  • At least 1 week since prior retinoids
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No concurrent medication to control arrhythmias
  • No concurrent medications that prolong or may prolong QTc interval
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  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: NCT00093821

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Tanya Trippett Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00093821     History of Changes
Other Study ID Numbers: NCI-2012-01456, 04-069, POETIC-MSKCC-04069, CDR0000391010, NCI-6323, MSKCC-04069, U01CA069856
Study First Received: October 6, 2004
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Osteosarcoma
Desmoplastic Small Round Cell Tumor
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neuroblastoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Rhabdomyosarcoma
Rhabdomyosarcoma, Embryonal
Sarcoma
Sarcoma, Ewing
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Myosarcoma
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Germ Cell and Embryonal

ClinicalTrials.gov processed this record on November 24, 2014