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:
Information provided by (Responsible Party):
Avillion Development 1 Limited
ClinicalTrials.gov Identifier:
NCT02130557
First received: May 1, 2014
Last updated: September 16, 2015
Last verified: September 2015
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 (CP) Chronic Myelogenous Leukemia (CML)

Resource links provided by NLM:


Further study details as provided by Avillion Development 1 Limited:

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 ] [ Designated as safety issue: No ]
    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 at 18 Months in the bosutinib treatment group with the imatinib treatment group [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • The duration of MMR in the bosutinib treatment group with the imatinib treatment group [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Duration of response is measured only for participants who initially respond to study medication.


Estimated Enrollment: 530
Study Start Date: June 2014
Estimated Study Completion Date: May 2020
Estimated 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
Active Comparator: Imatinib
Imatinib, 400 mg, oral administration once a day
Drug: Imatinib

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02130557

  Show 150 Study Locations
Sponsors and Collaborators
Avillion Development 1 Limited
  More Information

Responsible Party: Avillion Development 1 Limited
ClinicalTrials.gov Identifier: NCT02130557     History of Changes
Other Study ID Numbers: AV001 
Study First Received: May 1, 2014
Last Updated: September 16, 2015
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: National Health Surveillance Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: Danish Health and Medicines Authority
Finland: Finnish Medicines Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Mexico: Ministry of Health
Norway: Norwegian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Singapore: Health Sciences Authority
Slovakia: State Institute for Drug Control
South Korea: Korea Food and Drug Administration (KFDA)
Sweden: Medical Products Agency
Taiwan : Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Avillion Development 1 Limited:
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

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

ClinicalTrials.gov processed this record on July 25, 2016