Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00574873
Recruitment Status : Completed
First Posted : December 17, 2007
Results First Posted : November 4, 2012
Last Update Posted : January 8, 2019
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE December 13, 2007
First Posted Date  ICMJE December 17, 2007
Results First Submitted Date  ICMJE October 4, 2012
Results First Posted Date  ICMJE November 4, 2012
Last Update Posted Date January 8, 2019
Actual Study Start Date  ICMJE February 5, 2008
Actual Primary Completion Date August 31, 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2016)
Percentage of Participants With Complete Cytogenetic Response (CCyR) at Year 1 [ Time Frame: Year 1 (48 weeks) ]
Cytogenetic Response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0 percent (%) Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or less than (<) 1% breakpoint cluster region Abelson protooncogene (Bcr-Abl) fusion product among cells in a BM sample or peripheral blood sample when at least 200 cells were analyzed.
Original Primary Outcome Measures  ICMJE
 (submitted: December 14, 2007)
Cytogenetics response rate [ Time Frame: One year ]
Change History Complete list of historical versions of study NCT00574873 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2016)
  • Percentage of Participants With Major Molecular Response (MMR) at Year 1 [ Time Frame: Year 1 (48 weeks) ]
    Molecular response was assessed using Bcr-Abl transcript levels measured by reverse transcriptase polymerase chain reaction (RT-PCR) from peripheral blood. A MMR was defined as a ratio Bcr-Abl/Abl less than or equal to (≤) 0.1% on the international scale (greater than or equal to [≥] 3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts) with at least 3000 Abl analyzed.
  • Kaplan-Meier Estimate of Probability of Retaining CCyR at 192 Weeks [ Time Frame: 192 weeks ]
    The Kaplan-Meier curve was generated based the time from the first date of CCyR until the first date of confirmed loss of CCyR, objectively documented, for responders only. Participants without confirmed loss of CCyR were censored at the last valid cytogenetic assessment. CyR is based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or <1% Bcr-Abl fusion product among cells in a BM sample or peripheral blood sample when at least 200 cells were analyzed. The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided. Four years rate was displayed since the majority of participants had first CCyR by Year 1.
  • Kaplan-Meier Estimate of Probability of Retaining Complete Hematologic Response (CHR) at 192 Weeks [ Time Frame: 192 weeks ]
    The Kaplan-Meier curve was generated based on the first date of confirmed CHR until the first date of loss of CHR, objectively documented, for responders only. Participants without confirmed loss of response were censored at the last valid hematologic assessment. CHR must have been of at least 4 weeks in duration confirmed by 2 assessments at least 4 weeks apart and was defined as follows: white blood cells ≤ institutional upper limit of normal, no peripheral blasts or promyelocytes, myelocytes + metamyelocytes <5% in blood, absolute neutrophil count ≥1.0*10^9/L, platelets ≥100 but <450*10^9/L unless related to therapy, <20% basophils in blood and no extramedually involvement (including hepato- or splenomegaly). The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided. Four years rate was displayed since the majority of participants had first CHR by Year 1.
  • Kaplan-Meier Estimate of Probability of Retaining Derived MMR at 144 Weeks [ Time Frame: 144 weeks ]
    The Kaplan-Meier curve was generated based on the first date of MMR until the first date loss of MMR, objectively documented, for responders only. Participants without confirmed loss of response were censored at the last valid molecular assessment. Molecular response was assessed using Bcr-Abl transcript levels measured by RT-PCR from peripheral blood. MMR is defined as a ratio Bcr-Abl/Abl ≤0.1% on the international scale (≥3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts) with at least 3000 Abl analyzed. The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided. Three years rate was displayed since the majority of imatinib participants had first MMR by Year 2.
  • Cumulative Incidence of On-Treatment Transformation to Accelerated Phase (AP) or Blast Phase (BP) at 192 Weeks [ Time Frame: 192 weeks ]
    The cumulative incidence curve was generated based on the time from randomization to the first date of transformation to AP or BP while on study treatment adjusting for the competing risk of treatment discontinuation without transformation, for each participant. Criteria for transformation to AP: 15 to 29% blasts; ≥30% blasts + promyelocytes; ≥20% basophils in blood or bone marrow; platelets <100*10^9/L (not related to therapy), in blood. Criteria for transformation to BP: ≥30% blasts in blood or bone marrow and extramedullary involvement other than liver or spleen (example: chloromas). Time to transformation was calculated as weeks = ([date of first documented occurrence of the event - date of randomization] + 1)/7. If transformation was not obtained, censoring was at the last hematologic assessment or death (whichever was earliest). Participants who were not treated contributed time = 1 day/7. 95% confidence interval for the cumulative incidence is from Gray's method.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2007)
Major molecular response rate, duration of complete cytogenetics response, complete hematologic response, and major molecular response, time to transformation to accelerated and blast phases, population PK, comparative safety [ Time Frame: One year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML
Official Title  ICMJE A PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN SUBJECTS WITH NEWLY DIAGNOSED CHRONIC PHASE PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOGENOUS LEUKEMIA
Brief Summary Two-arm, randomized, open-label trial designed to evaluate the efficacy and safety of bosutinib alone compared to imatinib alone in subjects newly diagnosed with chronic phase Chronic Myelogenous Leukemia (CML). The primary endpoint is cytogenetic response rate at one year.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Myeloid Leukemia
Intervention  ICMJE
  • Drug: Bosutinib
    500 mg once daily, by mouth (tablet) with food preferably in the morning. Drug can be increased up to 600mg daily in case of lack of efficacy, and can be reduced to 300mg daily in case of toxicity. The drug will be given daily for up to 8 years until treatment failure, unacceptable toxicity, death or withdrawal of consent.
    Other Name: SKI 606
  • Drug: imatinib
    400 mg once daily, by mouth (tablet). Drug can be increased up to 600mg daily in case of lack of efficacy, and can be reduced to 300mg daily in case of toxicity. The drug will be given daily for up to 8 years until treatment failure, unacceptable toxicity, death or withdrawal of consent.
    Other Name: Gleevec
Study Arms  ICMJE
  • Experimental: 1
    Bosutinib
    Intervention: Drug: Bosutinib
  • Active Comparator: 2
    Imatinib
    Intervention: Drug: imatinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 29, 2012)
502
Original Estimated Enrollment  ICMJE
 (submitted: December 14, 2007)
412
Actual Study Completion Date  ICMJE May 27, 2015
Actual Primary Completion Date August 31, 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Cytogenetic diagnosis of chronic phase Ph+ CML diagnosed less than 6 months.
  • Diagnosis of CML chronic phase confirmed.
  • Adequate hepatic and renal function.
  • Able to take oral tablets.

Exclusion Criteria:

  • Exclusions include Philadelphia negative CML.
  • Prior anti-leukemia treatment.
  • Prior stem cell transplant.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile,   Russian Federation,   Argentina,   Belgium,   Brazil,   Canada,   China,   Colombia,   France,   Germany,   Hong Kong,   Hungary,   India,   Italy,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Mexico,   Poland,   Singapore,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Croatia,   Puerto Rico,   Slovenia
 
Administrative Information
NCT Number  ICMJE NCT00574873
Other Study ID Numbers  ICMJE 3160A4-3000
B1871008 ( Other Identifier: Alias Study Number )
2007-003780-50 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Wyeth is now a wholly owned subsidiary of Pfizer
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP