Phase IIb Study of Dasatinib Versus Imatinib in Patients With CML-CP Who Have Not Achieved an Early Optimal Response to Imatinib (Early switch)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01593254
First received: May 4, 2012
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

The study purpose is to test the hypothesis that patients with Chronic phase-Chronic Myeloid Leukemia (CP-CML) with BCR-ABL transcript level > 10% International Standard (IS) after 3 months of treatment with first line Imatinib 400mg will achieve a greater rate of major molecular response (MMR) by early switching to Dasatinib therapy 100mg once daily (QD) compared with continued treatment with Imatinib at any dose.


Condition Intervention Phase
Chronic Phase Chronic Myeloid Leukemia
Drug: Imatinib
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Randomized (2:1) Phase IIb Study of Dasatinib Versus Imatinib in Patients With Chronic Phase Chronic Myeloid Leukemia Who Have Not Achieved an Optimal Response to 3 Months of Therapy With 400 mg Imatinib

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Proportion of subjects who achieve Major Molecular Response (MMR) rate [ Time Frame: At 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Molecular Response over time - Proportion of randomized subjects who achieve MMR, MR4 and MR4.5 at each time-point from Day 1 treatment with first line Imatinib [ Time Frame: Months 6, 12, 18, 24, 36, 48 & 60 ] [ Designated as safety issue: No ]

    MR4 = 4- log reduction in BCR-ABL transcript from the standardized baseline [0.01% International Standard (IS)]

    MR4.5 = 4.5- log reduction in BCR-ABL transcript from the standardized baseline [0.0032% International Standard (IS)]


  • Cytogenetic Response over time - proportion of randomized subjects who achieve Complete Cytogenetic Response (CCyR) or major cytogenetic response (MCyR) at each time-point from Day 1 treatment with first line Imatinib [ Time Frame: Months 6, 12 & 18 ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) - PFS is defined as the time from randomization date to progression date or death date, whichever occurs first. Subjects who neither progress nor die, will be censored [ Time Frame: Months 12, 18, 24, 36, 48 & 60 ] [ Designated as safety issue: No ]
  • Overall Survival (OS)- OS is defined as the time from randomization date to death date. Subjects who have not died, will be censored on the last date they are known to be alive [ Time Frame: Months 12, 18, 24, 36, 48 & 60 ] [ Designated as safety issue: No ]
  • Time to and duration of Response - Time to MMR is the time between randomization date and first date that MMR criteria are satisfied [ Time Frame: Months 6, 15, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]
  • Time to and duration of Response - Time to MR4.5 is the time between randomization date and first date that MR4.5 criteria are satisfied [ Time Frame: Months 6, 12, 15, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]
  • Time to and duration of Response - Time to MR4 is the time between randomization date and first date that MR4 criteria are satisfied [ Time Frame: Months 6, 12, 15, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]
  • Time to and duration of Response - Time to CCyR is the time between randomization date and first date that CCyR criteria are satisfied [ Time Frame: Months 6, 12 and 18 ] [ Designated as safety issue: No ]
  • Time to and duration of Response - Time to MCyR is the time between randomization date and first date that MCyR criteria are satisfied [ Time Frame: Months 6, 12 and 18 ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: August 2012
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Imatinib (≥400 mg)
Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) depending on dose selected, up to 84 months
Drug: Imatinib
Other Name: Gleevac
Experimental: Arm 2: Dasatinib (100 mg)
Dasatinib 100 mg tablet by mouth QD up to 84 months
Drug: Dasatinib
Other Name: Sprycel

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • CP-CML Philadelphia chromosome positive (Ph+) patients with CHR but with BCR-ABL level >10% IS after 3 months of Imatinib 400 mg treatment. Imatinib monotherapy must have been started within 6 months of CP-CML diagnosis
  • Currently tolerating Imatinib 400 mg QD
  • Eastern Co-Operative Group (ECOG) performance status = 0 - 2
  • Adequate renal function defined as serum creatinine ≤ 3 times the institutional upper limit of normal (ULN)
  • Adequate hepatic function defined as:

    • Total Bilirubin ≤2.0 times institutional ULN
    • Alanine Aminotransferase (ALT) ≤2.5 times the institutional ULN
    • Aspartate Aminotransferase (AST) ≤2.5 times the institutional ULN
  • Serum Na, K, Mg, and total serum Ca or ionized Ca levels must be greater than or equal to the institutional lower limit of normal

Exclusion Criteria:

  • Accelerated Phase (AP)/ blast crisis (BP) diagnosis
  • Not in Complete Hematologic Response (CHR) by 3 month
  • Documented T315I/A, F317L, or V299L mutations
  • Prior Chronic Myeloid Leukemia (CML) treatment other than Imatinib
  • Serious, uncontrolled Medical condition
  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: NCT01593254

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 80 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01593254     History of Changes
Other Study ID Numbers: CA180-399, 2011-006181-41
Study First Received: May 4, 2012
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
European Union: European Medicines Agency
Canada: Ethics Review Committee
Canada: Health Canada
Korea: Ministry of Food and Drug Safety
Thailand: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
China: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Czech Republic: State Institute for Drug Control
Italy: The Italian Medicines Agency
Austria: Agency for Health and Food Safety
Argentina: Human Research Bioethics Committee
Austria: Austrian Medicines and Medical Devices Agency
Austria: Ethikkommission
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Institutional Review Board
Brazil: Ethics Committee
Brazil: National Committee of Ethics in Research
China: Ethics Committee
France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes
Italy: Ethics Committee
Poland: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Korea: Institutional Review Board
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Ethics Committee
Thailand: Ethical Committee
Thailand: Khon Kaen University Ethics Committee for Human Research

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
Dasatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014