17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00100997
Recruitment Status : Completed
First Posted : January 10, 2005
Last Update Posted : July 10, 2013
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin in treating patients with chronic phase chronic myelogenous leukemia that did not respond to imatinib mesylate.

Condition or disease Intervention/treatment Phase
Leukemia Drug: tanespimycin Phase 1

Detailed Description:



  • Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), in terms of frequency, severity, and duration of treatment-emergent adverse events, in patients with imatinib mesylate-resistant Philadelphia chromosome (Ph)-positive chronic phase chronic myelogenous leukemia.
  • Determine the pharmacokinetics of this drug and its primary metabolite (17-amino-17-demethoxygeldanamycin) in these patients.


  • Determine the hematologic response rate, in terms of WBC count, platelet count, and assessment of blast cells in peripheral blood, in patients treated with this drug.
  • Determine the cytogenic response rate, in terms of Ph-positive progenitor cells in the bone marrow, in patients treated with this drug.
  • Assess the effect of this drug on pharmacodynamic markers (i.e., CRKL phosphorylation, BCR-ABL kinase activity, and BCR-ABL, RAF kinase, and HSP70 expression) in these patients.

OUTLINE: This is an open label, dose-escalation, multicenter study.

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 15 minutes or 1 hour (depending on the dose administered) once on days 1, 4, 8, 11, 15, 18, 22, and 25. Treatment repeats every 28 days for up to 3 courses in the absence of unacceptable toxicity or disease progression. Eligible patients may receive additional courses of 17-AAG at the discretion of the investigator.

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 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 additional patients are treated at the MTD.

Patients are followed for 1 month.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Intravenously Administered CNF1010 )17-(Allylamino)-17-Demethoxygeldanamycin [17-AAG]) in Patients With Gleevec-Resistent Chronic Myelogenous Leukemia
Study Start Date : October 2004
Actual Study Completion Date : October 2006

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of chronic phase chronic myelogenous leukemia

    • Philadelphia chromosome (Ph)-positive disease
  • Hematologic resistence after treatment with imatinib mesylate (400 mg per day or maximum tolerated dose [MTD]) as defined by 1 of the following criteria:

    • Loss of complete hematologic response, defined as WBC count OR platelet count > upper limit of normal (ULN) on 2 separate occasions at least 2 weeks apart that cannot be attributed to other etiologies
    • Absolute increase of ≥ 30% in Ph-positive cells while on a stable dose of imatinib mesylate for at least 6 months* NOTE: *Patients meeting this criterion are not eligible for enrollment into the expanded MTD cohort
  • Less than 15% blasts in peripheral blood or bone marrow AND < 30% blasts and promyelocytes in peripheral blood or bone marrow



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 6 months


  • See Disease Characteristics


  • Bilirubin < 1.5 times ULN (3 mg/dL for patients with Gilbert's syndrome)
  • ALT or AST < 2 times ULN
  • No known hepatitis positivity


  • Creatinine < 1.5 times ULN OR
  • Creatinine clearance > 60 mL/min


  • No New York Heart Association class III or IV cardiac disease


  • No severe debilitating pulmonary disease, including any of the following:

    • Dyspnea at rest
    • Significant shortness of breath
    • Chronic obstructive pulmonary disease


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 month after study participation
  • No known HIV positivity
  • No psychological or social condition that would preclude study compliance
  • No addictive disorder that would preclude study compliance
  • No family problems that would preclude study compliance
  • No known allergy or sensitivity to soy or other excipient components of study drug
  • No other illness or condition that may affect safety of study treatment or evaluation of study endpoints


Biologic therapy

  • More than 2 weeks since prior interferon
  • No concurrent interferon


  • More than 2 weeks since prior cytarabine (4 weeks for doses > 100 mg)
  • More than 6 weeks since prior busulfan
  • No concurrent cytarabine
  • No concurrent hydroxyurea during the second study treatment course and beyond
  • No concurrent anagrelide during the second study treatment course and beyond

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • More than 2 days since prior imatinib mesylate
  • More than 1 week since prior and no concurrent drugs that alter metabolism by cytochrome P450 3A4, including the following:

    • Diltiazem
    • Nifedipine
    • Verapamil
    • Fluconazole
    • Itraconazole
    • Ketoconazole
    • Lovastatin
    • Simvastatin
    • Indinavir
    • Nelfinavir
    • Ritonavir
    • Alprazolam
    • Diazepam
    • Midazolam
    • Triazolam
    • Phenobarbital
    • Phenytoin
    • Carbamazepine
    • Azithromycin
    • Clarithromycin
    • Erythromycin
    • Rifampin
    • Rifamycin
    • Astemizole
    • Terfenidine
    • Amiodarone
    • Cimetidine
    • Cisapride
    • Cyclosporine
    • Grapefruit juice
    • Hypericum perforatum (St. John's wort)
    • Warfarin
  • More than 4 weeks since prior investigational drugs and recovered
  • No concurrent imatinib mesylate

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00100997

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Charles Sawyers, MD Jonsson Comprehensive Cancer Center Identifier: NCT00100997     History of Changes
Other Study ID Numbers: UCLA-0408048-01
CDR0000407499 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 10, 2005    Key Record Dates
Last Update Posted: July 10, 2013
Last Verified: May 2005

Keywords provided by National Cancer Institute (NCI):
chronic myelogenous leukemia, BCR-ABL1 positive
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases