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

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ClinicalTrials.gov Identifier: NCT00574873
Recruitment Status : Completed
First Posted : December 17, 2007
Results First Posted : November 5, 2012
Last Update Posted : October 17, 2016
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: Bosutinib Drug: imatinib Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 502 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Open-Label Study Of Bosutinib Versus Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
Study Start Date : February 2008
Actual Primary Completion Date : August 2010
Actual Study Completion Date : May 2015


Arm Intervention/treatment
Experimental: 1
Bosutinib
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

Active Comparator: 2
Imatinib
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


  3. 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.


  4. 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.


  5. 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.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00574873


  Show 171 Study Locations
Sponsors and Collaborators
Pfizer
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00574873     History of Changes
Other Study ID Numbers: 3160A4-3000
B1871008 ( Other Identifier: Alias Study Number )
2007-003780-50 ( EudraCT Number )
First Posted: December 17, 2007    Key Record Dates
Results First Posted: November 5, 2012
Last Update Posted: October 17, 2016
Last Verified: August 2016

Keywords provided by Pfizer:
Bosutinib
imatinib
CML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action