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A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

NCT02130557

Description:

Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive bosutinib or imatinib for the duration of the study.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
  • Official Title: A MULTICENTER PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIA

Clinical Trial IDs

  • ORG STUDY ID: AV001
  • SECONDARY ID: 2013-005101-31
  • SECONDARY ID: B1871053
  • NCT ID: NCT02130557

Conditions

  • Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive

Interventions

DrugSynonymsArms
BosutinibBosutinib
ImatinibImatinib

Purpose

Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive bosutinib or imatinib for the duration of the study.

Detailed Description

      The study will be open for enrollment until the planned number of approximately 500
      Philadelphia Chromosome Positive (Ph+) patients have been randomized (approximately 250 Ph+
      patients in each treatment arm; a total of approximately 530 Ph+ and Ph- patients). All
      patients will be treated and/or followed for approximately 5 years (240 weeks) after
      randomization until the study has closed. Patients who discontinue study therapy early due to
      disease progression or intolerance to study medication will continue to be followed yearly
      for survival for up to approximately 5 years (240 weeks) after randomization.
    

Trial Arms

NameTypeDescriptionInterventions
BosutinibExperimentalBosutinib, 400 mg, oral administration once a day
  • Bosutinib
ImatinibActive ComparatorImatinib, 400 mg, oral administration once a day
  • Imatinib

Eligibility Criteria

        Inclusion Criteria:

          1. Molecular diagnosis of CP CML of ≤ 6 months (from initial diagnosis).

          2. Adequate hepatic, renal and pancreatic function.

          3. Age ≥ 18 years.

        Exclusion Criteria:

          1. Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with
             the exception of hydroxyurea and/or anagrelide treatment, which are permitted for up
             to 6 months prior to study entry (signature of ICF) if suitably approved for use in
             the subject's region.

          2. Any past or current Central Nervous System (CNS) involvement, including leptomeningeal
             leukemia.

          3. Extramedullary disease only.

          4. Major surgery or radiotherapy within 14 days of randomization.

          5. History of clinically significant or uncontrolled cardiac disease.

          6. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic
             hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence
             of decompensated liver disease. Patients with resolved Hepatitis B can be included.

          7. Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative
             Colitis, or prior total or partial gastrectomy.

          8. History of another malignancy within 5 years with the exception of basal cell
             carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered
             adequately treated and currently in complete remission for at least l2 months.

          9. Current, or recent (within 30 days, or 5 half-lives of investigational product)
             participation in other clinical trials of investigational agents and/or containing
             interventional procedures deemed contrary to the objectives and conduct of this trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Major Molecular Response (MMR) at Month 12
Time Frame:Month 12
Safety Issue:
Description:MMR was defined as a ratio of breakpoint cluster region to abelson (BCR-ABL/ABL) less than or equal to (<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to [>=] 3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts [>=3000 ABL required]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The percentage of participants with MMR at Month 12 are reported.

Secondary Outcome Measures

Measure:Percentage of Participants With Major Molecular Response (MMR) Up to Month 18
Time Frame:Up to Month 18
Safety Issue:
Description:MMR was defined as a ratio of BCR-ABL/ABL <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts [>=3000 ABL required]) by quantitative RT-qPCR. The percentage of participants with MMR for up to Month 18 are reported.
Measure:Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48
Time Frame:Month 48
Safety Issue:
Description:The Kaplan-Meier curve was generated based on the first date of MMR until the date of the confirmed loss of MMR or censoring, objectively documented, for responders only. Confirmed loss of MMR was BCR-ABL/ABL IS ratio >0.1% in association with a >=5-fold increase in BCR-ABL/ABL IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase (AP) or blast phase (BP) CML.
Measure:Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12
Time Frame:Up to Month 12
Safety Issue:
Description:Complete Cytogenetic Response (CCyR) was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow (BM) aspirate. 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 MMR if no BM was available. The percentage of participants with CCyR for up to Month 12 are reported.
Measure:Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48
Time Frame:Month 48
Safety Issue:
Description:The Kaplan-Meier curve was generated based on the first date of CCyR until the date of the confirmed loss of CCyR or censoring, objectively documented, for responders only. Confirmed loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, PD or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to AP or BP CML.
Measure:Cumulative Incidence of Event Free Survival (EFS) Events
Time Frame:Up to Month 60
Safety Issue:
Description:EFS was defined as time from randomization to death due to any cause, transformation to AP or BP at any time, confirmed loss of complete hematologic response (CHR), confirmed loss of CCyR or censoring. Loss of CHR was defined as a hematologic assessment of non-CHR (chronic phase, AP, or BP) confirmed by 2 assessments at least 4 weeks apart. Loss of CHR was defined as appearance of any of the following: WBC count that rises to >20.0*10^9/L, platelet count rises to >=600*10^9/L, appearance of palpable spleen or other extramedullary involvement proven by biopsy, appearance of 5% myelocytes in peripheral blood, appearance of blasts or promyelocytes in peripheral blood. Loss of CCyR was defined as at least 1 Ph+ metaphase from analysis of <100 metaphases confirmed by follow up cytogenetic analysis after 1 month. Cumulative incidence of EFS was defined as percentage of participants with EFS event at Month 60 and was adjusted for competing risk of treatment discontinuation without event.
Measure:Overall Survival (OS) Rate
Time Frame:Up to Month 60
Safety Issue:
Description:OS was defined as the time (in months) from randomization to the occurrence of death due to any cause or censoring. Kaplan-meier analysis was used for determination of OS. Percentage of participants who were alive were estimated in this outcome measure.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Pfizer

Trial Keywords

  • Leukemia
  • Myelogenous
  • Chronic
  • BCR-ABL Positive
  • Bosutinib
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Philadelphia Chromosome
  • Neoplasms by Histologic Type
  • Bone Marrow Diseases
  • Hematologic Diseases
  • Translocation, Genetic
  • Pathologic Processes
  • Imatinib
  • Therapeutic Uses
  • Pharmacologic Actions
  • Molecular Mechanisms of Pharmacological Action

Last Updated

May 18, 2021