A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
Condition: Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
Intervention: Bosutinib; Imatinib
Intervention description: Bosutinib (Bosulif®) is an orally bioavailable, potent, multi-targeted, dual Src-Abl tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia positive (Ph+) chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with other TKI inhibitor therapy.[1] This study will investigate the use of bosutinib as first-line treatment for patients with Ph+ CP CML.; Imatinib mesylate (referred to in this protocol as imatinib) is an inhibitor of the BCR-ABL kinase and been the standard first-line therapy for patients with chronic-phase CML. Imatinib was granted approval by the European Commission in November 2001 and by the FDA in December 2002 for the treatment of newly diagnosed patients with CP Ph+ CML based on results from the IRIS trial.
Imatinib is considered the standard of care for both first-line and later line settings, and consequently is an appropriate active comparator.
Intervention MeSH terms: Imatinib Mesylate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: NOTE: Value was Open Label in old format; This study has an open-label design. Although most efficacy studies have a double blind design, this is not feasible in this trial, due to the complexity of the dose reduction and dose escalation schemes with tablets of various sizes, dosage strengths, as well as the number of tablets that would be required daily. However, the opportunity for bias is mitigated by the use of objective outcome measures (MMR, CCyR, CHR). The Investigators will be instructed to ensure that laboratory/pathology personnel are blinded to treatment information. For these reasons, an open-label, randomized study is appropriate.
Enrollment: 536.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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

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.