Imatinib Mesylate and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Chronic Myelogenous Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00066326
First received: August 6, 2003
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as 17-N-allylamino-17-demethoxygeldanamycin use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate with chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given together with imatinib mesylate in treating patients with chronic myelogenous leukemia.


Condition Intervention Phase
Leukemia
Drug: imatinib mesylate
Drug: tanespimycin
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study Of The Combination Of 17-AAG And Imatinib Mesylate (Gleevec) In Patients With Blastic Phase, Accelerated Phase Of Chronic Mesylate Leukemia (CML) Or Patients With Chronic Phase CML Who Have Not Achieved A Cytogenetic Response With Imatinib Mesylate

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Study Start Date: June 2003
Study Completion Date: September 2005
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with imatinib mesylate in patients with chronic myelogenous leukemia.
  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

Patients receive oral imatinib mesylate on days 1-21 and 17-AAG IV over 1 hour on days 1, 4, 8, and 12. Courses repeat every 21 days 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 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 6-10 patients receives treatment at the recommended phase II dose.

PROJECTED ACCRUAL: Approximately 21-42 patients will be accrued for this study within 1.5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of chronic myelogenous leukemia, including any of the following phases:

    • Blastic phase

      • Greater than 30% blasts in the peripheral blood or bone marrow
      • Previously untreated disease OR refractory to or relapsed after most recent therapy
    • Accelerated phase, defined by 1 of the following:

      • At least 15, but less than 30%, blasts in the peripheral blood or bone marrow
      • At least 30% blasts and promyelocytes in the peripheral blood or bone marrow
      • Greater than 20% peripheral blood basophilia
    • Chronic phase

      • No major cytogenetic response (less than 65% Philadelphia chromosome negative) after 12 months of prior imatinib mesylate therapy
  • Philadelphia chromosome positive by routine cytogenetics

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 3 months

Hematopoietic

  • Not specified

Hepatic

  • Bilirubin no greater than 1.5 mg/dL
  • ALT and AST no greater than 2.5 times upper limit of normal

Renal

  • Creatinine less than 1.5 mg/dL

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known allergy to eggs
  • Able to swallow pills
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other concurrent uncontrolled medical illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior stem cell transplantation

Chemotherapy

  • More than 4 weeks since prior chemotherapy (except hydroxyurea or anagrelide) (at least 6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

  • Not specified

Radiotherapy

  • More than 4 weeks since prior radiotherapy

Surgery

  • No prior liver, kidney, or lung transplantation
  • More than 14 days since prior major surgery (e.g., thoracotomy or intra-abdominal surgery)

Other

  • Prior imatinib mesylate administered within the past 4 weeks is allowed
  • No concurrent tacrolimus or cyclosporine as immunosuppressive agents
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent agents that alter CYP3A4 activity, including any of the following:

    • Grapefruit juice
    • Ketoconazole
    • Fluconazole
    • Itraconazole
    • Erythromycin
    • Clarithromycin
    • Cimetidine
    • Terfenadine
    • Astemizole
    • HIV protease inhibitors (e.g., indinavir and nelfinavir)
  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: NCT00066326

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Charles A. Schiffer, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00066326     History of Changes
Other Study ID Numbers: CDR0000315521, U01CA062487, P30CA022453, WSU-C-2599, NCI-5932
Study First Received: August 6, 2003
Last Updated: April 3, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
blastic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014