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Imatinib Mesylate or Dasatinib in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia
This study is ongoing, but not recruiting participants.
First Received: October 3, 2003   Last Updated: April 14, 2009   History of Changes
Sponsors and Collaborators: Southwest Oncology Group
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070499
  Purpose

RATIONALE: Imatinib mesylate or dasatinib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: This randomized phase II trial is studying imatinib mesylate at two different doses and dasatinib to see how well they work in treating patients with previously untreated chronic phase chronic myelogenous leukemia.


Condition Intervention Phase
Leukemia
Drug: dasatinib
Drug: imatinib mesylate
Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic
Drug Information available for: Imatinib Imatinib mesylate Dasatinib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Phase IIb Study Of Molecular Responses To Imatinib At Standard Or Increased Doses or Dasatinib (NSC-732517) For Previously Untreated Patients With Chronic Myelogenous Leukemia (CML) In Chronic Phase

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

Primary Outcome Measures:
  • Molecular response at 12 months [ Designated as safety issue: No ]
  • Hematological response [ Designated as safety issue: No ]
  • Cytogenetic response (complete and partial response) measured on bone marrow at baseline, 6 and 12 months [ Designated as safety issue: No ]
  • Prognostic effects [ Designated as safety issue: No ]
  • Changes in gene expression at pre-treatment and relapse [ Designated as safety issue: No ]
  • Frequency and severity of toxic effects [ Designated as safety issue: Yes ]
  • Overall and relapse-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: August 2004
Estimated Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator
Patients receive oral imatinib mesylate once daily.
Drug: imatinib mesylate
Given orally
Arm II: Experimental
Patients receive oral imatinib mesylate twice daily.
Drug: imatinib mesylate
Given orally
Arm III: Experimental
Patients receive oral dasatinib twice daily.
Drug: dasatinib
Given orally

Detailed Description:

OBJECTIVES:

  • Compare the rate of molecular response, as measured by the decrease in bcr-abl transcripts after 12 months of treatment, in patients with previously untreated chronic phase chronic myelogenous leukemia treated with imatinib mesylate at standard vs increased dose or dasatinib.
  • Test whether increasing doese of imatinib mesylate from 400 mg/day to 800 mg/day increases molecular response rate (as measured by decrese in bcr-abl transcript after 12 months of treatment) in these patients.
  • Compare rates of cytogenetic and hematologic response in patients treated with these regimens.
  • Compare, preliminarily, the prognostic effects of der(9) and der(22) chromosomal deletions for response in patients treated with these regimens.
  • Compare, preliminarily, changes in gene expression at pre-treatment vs at relapse or progression in patients treated with these regimens.
  • Compare the frequency and severity of the toxic effects of these regimens in these patients.
  • Compare, preliminarily, the overall survival and relapse-free survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Hasford risk category (low vs intermediate vs high). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive oral imatinib mesylate once daily.
  • Arm II: Patients receive oral imatinib mesylate twice daily.
  • Arm III: Patients receive oral dasatinib twice daily. In all arms, treatment continues for 5 years in the absence of disease progression or unacceptable toxicity.

Patients are followed for up to 5 years.

PROJECTED ACCRUAL: A total of 335 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of chronic phase chronic myelogenous leukemia (CML) by bone marrow aspiration, biopsy, and peripheral blood counts, meeting criteria for

    1 of the following:

    • Philadelphia chromosome-positive* or presence of the variants of the (9;22) translocation by cytogenetics or fluorescent in situ hybridization

      • Secondary chromosomal abnormalities (in addition to the Philadelphia chromosome) allowed
    • bcr-abl positive* by reverse transcription polymerase chain reaction NOTE: *First cytogenetic or molecular analysis performed within the past 180 days to confirm status
  • Must be enrolled on SWOG-9007 (SWOG institutions only) and SWOG-S9910

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • No significant bleeding disorder unrelated to cancer including:

    • Congenital bleeding disorders (e.g., von Willebrand's disease)
    • Acquired bleeding disorder within the past year (e.g., acquired anti-factor VIII antibodies)

Hepatic

  • Bilirubin no greater than 2.0 times upper limit of normal (ULN)
  • AST or ALT no greater than 2.0 times ULN

Renal

  • Not specified

Cardiovascular

  • No cardiac symptoms including any of the following:

    • Uncontrolled angina
    • Congestive heart failure or myocardial infarction within the past 6 months
    • Diagnosed or suspected congenital long QT syndrome
    • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
    • Prolonged QTc interval on electrocardiogram (> 450 msec)
    • Uncontrolled hypertension

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No other concurrent anticancer biologic agents

Chemotherapy

  • No prior chemotherapy for peripheral blood stem cell mobilization

    • Prior collection of unmobilized peripheral blood stem cells allowed
  • No other concurrent anticancer chemotherapy

    • Concurrent hydroxyurea and/or anagrelide to control blood counts allowed provided it is only administered during the first 28 days of study therapy and for no more than 28 additional days after study therapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No concurrent anticancer radiotherapy

Surgery

  • More than 28 days since prior major surgery and recovered

Other

  • No prior treatment for CML (except hydroxyurea and/or anagrelide)
  • No concurrent therapeutic anticoagulation with warfarin

    • Concurrent therapeutic anticoagulation with low-molecular weight heparin allowed
    • Concurrent low-dose warfarin for prophylaxis to prevent catheter thrombosis allowed (arm III only)
  • No concurrent drugs* that have a risk of causing Torsades de Pointe including (arm III patients only):

    • Quinidine, procainamide, disopyramide
    • Amiodarone, sotalol, ibutilide, dofetilide
    • Erythromycin, clarithromycin
    • Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
    • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone
    • Halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine NOTE: *Patients who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug prior to first dose of dasatinib
  • No concurrent drugs that irreversibly inhibit platelet function, including any of the following (arm III only):

    • Aspirin

      • Patients who have discontinued aspirin must have a wash-out period of at least 7 days for low-dose aspirin (< 325 mg/day) or 14 days for high-dose aspirin (> 325 mg/day) prior to first dose of dasatinib
    • Dipyridamole
    • Epoprostenol
    • Eptifibatide
    • Clopidogrel
    • Cilostazol
    • Abciximab
    • Ticlopidine
  • No other concurrent anticancer agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00070499

  Show 230 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Eastern Cooperative Oncology Group
Investigators
Investigator: Brian J. Druker, MD Oregon Health and Science University
Investigator: Marilyn L. Slovak, PhD Beckman Research Institute
Investigator: Peter D. Emanuel, MD Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group - Group Chair's Office ( Laurence H. Baker )
Study ID Numbers: CDR0000334588, SWOG-S0325, ECOG-S0325
Study First Received: October 3, 2003
Last Updated: April 14, 2009
ClinicalTrials.gov Identifier: NCT00070499     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia

Study placed in the following topic categories:
Imatinib
Philadelphia Chromosome
Leukemia
Hematologic Diseases
Dasatinib
Myeloproliferative Disorders
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chronic Myelogenous Leukemia
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid
Bone Marrow Diseases
Protein Kinase Inhibitors

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

ClinicalTrials.gov processed this record on May 07, 2009