Imatinib Mesylate or Dasatinib in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00070499
First received: October 3, 2003
Last updated: October 7, 2013
Last verified: October 2013
  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. Imatinib mesylate or dasatinib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.


Condition Intervention Phase
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Chronic Phase Chronic Myelogenous Leukemia
Drug: dasatinib
Drug: imatinib mesylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Molecular Response Rate at 12 Months [ Time Frame: pretreatment and after 12 months of treatment ] [ Designated as safety issue: No ]
    Median value of baseline bcr-abl/bcr ratio from pretreatment was used as the baseline value for assessing each patient's molecular response. Molecular response criteria were: 1) not failed treatment on or before 12-month evaluation; 2) met criteria for hemalotogic response; 3) bcr-abl/bcr ration at 12-months must be 10,000 times smaller than the pretreatment ratio.


Secondary Outcome Measures:
  • Hematologic Response [ Time Frame: 1 month after starting treatment ] [ Designated as safety issue: No ]
    Hematologic response assesses whether patients' blood counts return to normal

  • 2-year Overall Survival (OS) [ Time Frame: Every three months for the first year, every six months in years 2 and 3, and annually for years 4 and 5 ] [ Designated as safety issue: No ]
    Overall survival was measured from the date of registration to study until death from any cause with observations censored at the date of last contact for patients last known to be alive.

  • Two Year Relapse-free Survival [ Time Frame: every 3 months for the first year, every six months for years 2 and 3, annually for years 4 and 5 ] [ Designated as safety issue: No ]
    Relapse-free survival is measured from the date of documented (possibly unconfirmed) hematologic complete remission until loss of hematologic complete remission or death from any cause. Observations are censored at the date of last contact for patients last known to be alive with report of loss of hematologic complete remission.

  • Toxicity [ Time Frame: Patients were assessed for adverse events monthly every 4 weeks for the first year, every 6 months for years 2 and 3, and annually for years 4 and 5. ] [ Designated as safety issue: Yes ]
    Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event


Enrollment: 400
Study Start Date: August 2004
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (once daily imatinib mesylate)
Patients receive oral imatinib mesylate once daily.
Drug: imatinib mesylate
Given PO
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (twice daily imatinib mesylate)
Patients receive oral imatinib mesylate twice daily.
Drug: imatinib mesylate
Given PO
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (dasatinib)
Patients receive oral dasatinib twice daily.
Drug: dasatinib
Given orally (PO)
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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.

II. Test whether increasing dose of imatinib mesylate from 400 mg/day to 800 mg/day increases molecular response rate (as measured by decrease in bcr-abl transcript after 12 months of treatment) in these patients.

III. Compare rates of cytogenetic and hematologic response in patients treated with these regimens.

IV. Compare, preliminarily, the prognostic effects of der(9) and der(22) chromosomal deletions for response in patients treated with these regimens.

V. Compare, preliminarily, changes in gene expression at pre-treatment vs at relapse or progression in patients treated with these regimens.

VI. Compare the frequency and severity of the toxic effects of these regimens in these patients.

VII. Compare, preliminarily, the overall survival and relapse-free survival of patients treated with these regimens.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive oral imatinib mesylate once daily. Patients continue daily treatment for up to 5 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive oral imatinib mesylate twice daily. Patients continue daily treatment for up to 12 months in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive oral dasatinib twice daily. Patients continue daily treatment for up to 15 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 15 years.

  Eligibility

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

Criteria:

  • 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]
  • 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
  • Must be enrolled on SWOG-9007 (SWOG institutions only) and SWOG-S9910
  • 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)
  • Bilirubin no greater than 2.0 times upper limit of normal (ULN)
  • AST or ALT no greater than 2.0 times ULN
  • 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
  • Zubrod 0-2
  • Not pregnant or nursing

    • Fertile patients must use effective contraception
  • No other concurrent anticancer biologic agents
  • 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
  • No concurrent anticancer radiotherapy
  • More than 28 days since prior major surgery and recovered
  • 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
    • Pepridil
    • 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 299 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Brian Druker Southwest Oncology Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070499     History of Changes
Other Study ID Numbers: NCI-2009-00764, NCI-2009-00764, S0325, S0325, U10CA032102
Study First Received: October 3, 2003
Results First Received: June 5, 2012
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 16, 2014