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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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02130557
First Posted: May 5, 2014
Last Update Posted: December 14, 2017
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.
Information provided by (Responsible Party):
Pfizer
  Purpose
Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive bosutinib or imatinib for the duration of the study.

Condition Intervention Phase
Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive Drug: Bosutinib Drug: Imatinib Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
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.
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • The proportion of participants with Major Molecular Response (MMR) at 12 Months in the bosutinib arm with that of the imatinib arm [ Time Frame: 12 Months ]
    MMR is defined as <0.1%Bcr-Abl1 on the International Scale (IS) by Real Time Quantitative Polymerase Chain Reaction (RT-PCR)


Secondary Outcome Measures:
  • The proportion of participants with MMR by 18 Months in the bosutinib treatment group with the imatinib treatment group [ Time Frame: 18 Months ]
    For the analysis of MMR by 18 months a patient is counted as a response if MMR occurs at or before the 18 months, even if MMR is subsequently lost at or before the 18 months. A patient never achieving MMR at or before 18 months is deemed a non-response.

  • The duration of MMR in the bosutinib treatment group with the imatinib treatment group [ Time Frame: 5 Years ]
    Duration of MMR is measured only for participants who initially respond to study medication.

  • The proportion of participants with Complete Cytogenetic Response (CCyR) by 12 Months in both treatment groups [ Time Frame: 12 Months ]
    CCyR is defined as absence of detectable Ph chromosomes in bone marrow aspirate

  • The duration of CCyR in both treatment groups [ Time Frame: 5 Years ]
    Duration of response is measured only for participants who initially respond to study medication.

  • The event free survival (EFS) in both treatment groups. [ Time Frame: 5 Years ]

    Event free survival (EFS) defined as the time without occurrence of:

    1. Death due to any cause.
    2. Transformation to AP or BP at any time.
    3. Loss of CHR.

      • Loss of CHR is defined as the appearance of any of the following, confirmed by a second determination ≥4 weeks later (unless associated with CML-related treatment discontinuation):
      • WBC count that rises to >20.0 x 109/L.
      • Platelet count that rises to ≥600 x 109/L.
      • Appearance of palpable spleen or other extramedullary involvement proven by biopsy.
      • Appearance of 5% myelocytes in the peripheral blood.
      • Appearance of blasts or promyelocytes in the peripheral blood.

  • The overall survival (OS) in both treatment groups. [ Time Frame: 5 years ]
    Overall survival (OS), defined as the time from randomization to the occurrence of death due to any cause.

  • The population pharmacokinetics (PK) and correlations between trough concentrations of bosutinib and key efficacy and safety parameters.of bosutinib administered once daily. [ Time Frame: 84 Days ]
    The objectives of the population PK analysis are 1) to develop a population PK model which describes the PK of bosutinib in this patient population, 2) to evaluate the influence of demographic and clinical covariates on the exposure of bosutinib, 3) to explore the relationship between trough concentrations of bosutinib with clinical safety (drug related adverse effects such as GI AEs, and any other major AEs) and efficacy endpoints.

  • The safety profile of bosutinib and imatinib treatments. [ Time Frame: 5 years ]
    Safety will be assessed on an ongoing basis by physical examination including measurement of vital signs, laboratory assessments, standard safety evaluations (electrocardiograms [ECGs] for monitoring of QTc interval changes and echocardiograms/MUGA scans for monitoring ventricular function) and recording of adverse events (AEs) and serious adverse events (SAEs). Adverse events will be graded according to the NCI CTC version 4. Discontinuations due to AEs will be considered the main comparative safety endpoint for AEs. In addition standard laboratory assessments will be performed.


Enrollment: 535
Actual Study Start Date: July 2014
Estimated Study Completion Date: August 2020
Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bosutinib
Bosutinib, 400 mg, oral administration once a day
Drug: Bosutinib
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.
Active Comparator: Imatinib
Imatinib, 400 mg, oral administration once a day
Drug: Imatinib

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.


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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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): NCT02130557


  Show 193 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02130557     History of Changes
Other Study ID Numbers: AV001
2013-005101-31 ( EudraCT Number )
B1871053 ( Other Identifier: Alias Study Number )
First Submitted: May 1, 2014
First Posted: May 5, 2014
Last Update Posted: December 14, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:
Bosutinib
Leukemia
Myelogenous
Chronic
BCR-ABL Positive
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

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