Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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

Further Study Information

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:

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.

After completion of study treatment, patients are followed for up to 5 years.

Eligibility 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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Brian Druker

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00070499
Information obtained from ClinicalTrials.gov on April 01, 2013

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