A Study of Dasatinib vs. High-Dose Imatinib (600 mg) in Patients With Chronic Phase Chronic Myeloid Leukemia (CML) Who Failed to Achieve Complete Cytogenetic Response After 3-18 Months of Imatinib Therapy

An Open-Label Randomized Phase III Study of Dasatinib vs. High-Dose (600 mg) Imatinib Mesylate in the Treatment of Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Are Imatinib Failures or Who Have Had a Suboptimal Response After 3-18 Months of Therapy With 400 mg Imatinib

The purpose of this clinical research study is to compare the rate of complete cytogenetic response of dasatinib to imatinib therapy at 6 months after randomization in chronic phase CML patients. The safety of this treatment will also be studied.

Study Overview

• Status: Terminated
• Conditions: Leukemia
• Intervention / Treatment: Drug: Dasatinib; Drug: Imatinib

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Dr. Marshall Schreeder
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Local Institution
  • California
    • Alhambra, California, United States, 91801
      • Local Institution
    • Anaheim, California, United States, 92801
      • Local Institution
    • Beverly Hills, California, United States, 90211
      • Local Institution
    • Fullerton, California, United States, 92835
      • Local Institution
    • La Jolla, California, United States, 92093
      • Local Institution
    • La Verne, California, United States, 91750
      • Local Institution
    • Long Beach, California, United States, 90813
      • Local Institution
    • Los Angeles, California, United States, 90033
      • Local Institution
    • Los Angeles, California, United States, 90095
      • Local Institution
    • Los Angeles, California, United States, 90048
      • Local Institution
    • Northridge, California, United States, 91325
      • Local Institution
    • Oxnard, California, United States, 93030
      • Local Institution
    • Redondo Beach, California, United States, 90277
      • Local Institution
    • San Francisco, California, United States, 94143
      • Local Institution
    • Santa Maria, California, United States, 93454
      • Local Institution
    • Stanford, California, United States, 94305
      • Local Institution
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Local Institution
    • Jacksonville, Florida, United States, 32207
      • Local Institution
    • Orlando, Florida, United States, 32806
      • M.D. Anderson Cancer Center Orlando
    • Pembroke Pines, Florida, United States, 33028
      • Local Institution
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Local Institution
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Local Institution
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Local Institution
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Local Institution
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Local Institution
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Local Institution
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Local Institution
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Local Institution
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution
  • New York
    • Buffalo, New York, United States, 14263
      • Local Institution
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Local Institution
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Local Institution
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Local Institution
    • Tulsa, Oklahoma, United States, 74136
      • Local Institution
  • Pennsylvania
    • Baltimore, Pennsylvania, United States, 21229
      • Local Institution
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution
  • South Carolina
    • Sumter, South Carolina, United States, 29150
      • Santee Hematology/Oncology
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution
    • Houston, Texas, United States, 77030
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women ≥18 years diagnosed with Chronic Phase Philadelphia chromosome positive (CP Ph+) CML who have failed to achieve CCyR after 3-18 months of therapy with imatinib 400 mg
• Treatment initiation with imatinib 400 mg within 6 months of initial CML diagnosis
• Able to tolerate chronic administration of imatinib at the highest dose (400-600 mg) the subject has received in the past
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
• Adequate hepatic and renal function

Exclusion Criteria:

• Eligible and willing to undergo immediate autologous/allogeneic stem cell transplant
• Previous diagnosis of accelerated/blast crisis CML
• Subjects with clonal evolution in Ph+ cells observed in ≥2 metaphases
• Previous documentation of T315I mutation
• Uncontrolled or significant cardiovascular disease
• Serious uncontrolled medical disorder/active infection
• History of significant bleeding disorder unrelated to CML
• Intolerance to imatinib ≥400 mg
• Concurrent malignancies other than CML

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; 50-180 mg once daily (QD)	Drug: Dasatinib; Tablets, Oral, Once daily, 5-7 years; Other Names: Sprycel®
Active Comparator: B; 200-800 mg QD	Drug: Imatinib; Tablets, Oral, Once daily, 5-7 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Cytogenetic Response (CCyR) Rate at Month 6	Cytogenetic Response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. The criteria for CCyR is 0% Ph+ metaphases among cells in a bone marrow sample.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Molecular Response (MMR) Rates	MMR is defined as a 3-log reduction in BCR-ABL gene transcripts from a standardized baseline. Reductions in BCR-ABL transcripts on logarithmic scale are calculated based on the absolute values expressed as percent of ratio of BCR-ABL gene transcripts to the control gene. In this study,ABL was used as the control gene.	Month 3, Month 6, Month 12, Month 24 and Month 36
CCyR Rates	CyR is based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. The criteria for CCyR is 0% Ph+ metaphases among cells in a bone marrow sample.	Month 3, Month 12, Month 24 and Month 36
Estimate Time to MMR and CCyR	Time to MMR is defined as the time from first treatment dose until measurement criteria are first met for MMR. Time to MMR is computed only for subjects who achieved a MMR. Time to CCyR is defined as the time from first treatment dose until measurement criteria are first met for CCyR. Time to CCyR is computed only for subjects who achieved a CCyR.	throughout the study
Progression Free Survival (PFS)	PFS=time from randomization until progression or death. Participants who died without progression=progression on date of death. Participants who neither progressed nor died were censored on date of last hematologic assessment. Participants who did not receive study treatment and neither progressed nor died were censored on date of randomization.	at 36 months
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs	An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.	From 2 weeks prior to randomization through Month 36. At least every 4 weeks until all study-related toxicities resolve to baseline, stabilize, or are deemed irreversible.
Duration of CCyR and MMR	Duration of CCyR computed for subjects with CCyR as best response; measured from time the criteria are first met for CCyR until date of progression or death. Duration of MMR computed for subjects with MMR as best response; measured from time the criteria are first met for MMR until date the MMR was first lost, disease progression or death.	Throughout the study
Best MMR Rates	MMR is defined as a 3-log reduction in BCR-ABL gene transcripts from a standardized baseline. Reductions in BCR-ABL transcripts on logarithmic scale are calculated based on the absolute values expressed as % of ratio of BCR-ABL gene transcripts to the control gene. In this study, ABL was used as the control gene.	throughout study

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: August 9, 2006
• First Submitted That Met QC Criteria: August 9, 2006
• First Posted (Estimate): August 10, 2006

Study Record Updates

• Last Update Posted (Estimate): November 20, 2009
• Last Update Submitted That Met QC Criteria: November 18, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: Leukemia (chronic myeloid leukemia - chronic phase)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate; Dasatinib
• Other Study ID Numbers: CA180-044