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

April 3, 2013 updated by: Barbara Ann Karmanos Cancer Institute

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Charles A. Schiffer, MD, Barbara Ann Karmanos Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2003

Primary Completion (Actual)

October 1, 2004

Study Completion (Actual)

September 1, 2005

Study Registration Dates

First Submitted

August 6, 2003

First Submitted That Met QC Criteria

August 6, 2003

First Posted (Estimate)

August 7, 2003

Study Record Updates

Last Update Posted (Estimate)

April 5, 2013

Last Update Submitted That Met QC Criteria

April 3, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000315521
  • P30CA022453 (U.S. NIH Grant/Contract)
  • U01CA062487 (U.S. NIH Grant/Contract)
  • WSU-C-2599
  • NCI-5932

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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