S0325 Imatinib Mesylate or Dasatinib in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia - Full Text View

Sponsor:	Southwest Oncology Group
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group
Information provided by:	Southwest Oncology Group
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

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:

MedlinePlus related topics: Cancer Chronic Myeloid Leukemia Leukemia

Drug Information available for: Imatinib Imatinib mesylate Dasatinib

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

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
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients receive oral imatinib mesylate once daily.	Drug: imatinib mesylate Given orally
Experimental: Arm II Patients receive oral imatinib mesylate twice daily.	Drug: imatinib mesylate Given orally
Experimental: Arm III 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

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Investigators

Study Chair:	Brian J. Druker, MD	OHSU Knight Cancer Institute
Principal Investigator:	Marilyn L. Slovak, PhD	Beckman Research Institute
Principal Investigator:	Peter D. Emanuel, MD	University of Alabama at Birmingham

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Laurence H. Baker, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00070499 History of Changes
Other Study ID Numbers:	CDR0000334588, U10CA032102, S0325, S0325
Study First Received:	October 3, 2003
Last Updated:	July 19, 2011
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:

chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia

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 February 12, 2012