A Study of Dasatinib in Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00482703
First received: June 4, 2007
Last updated: November 30, 2010
Last verified: November 2010
  Purpose

The objective is to evaluate the cytogenetic response to Dasatinib (BMS-354825) administered for 24 weeks in subjects with Imatinib resistant or intolerant chronic phase chronic myeloid leukemia (CML) once daily (QD) or twice daily. (BID)


Condition Intervention Phase
Myeloid Leukemia, Chronic
Drug: Dasatinib
Drug: dasatinib
Phase 1
Phase 2

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 Randomized, Multicenter, Open-label Phase II Study of Dasatinib (BMS-354825) Administered Orally at a Dose of 50mg Twice Daily or 100mg Once Daily in Subjects With Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia Who Are Resistant or Intolerant to Imatinib

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Cytogenetic responses (CyR) are based on the percentage of Philadelphia-positive (Ph+) metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), and Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).


Secondary Outcome Measures:
  • Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment [ Time Frame: Throughout study period to last observation. Dosing period=6 months; if beneficial, medication may continue in the extension period (ending in January 2009). Last observation=30 days past last dosing day or the discontinuation day. ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

  • Complete Hematologic Response (CHR) in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils < 20%; no extramedullary involvement. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.

  • Time to Major Cytogenetic Response (MCyR) [ Time Frame: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met ] [ Designated as safety issue: No ]
    Time to MCyR is defined as the time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met. MCyR = a complete and a partial cytogenetic response (CyR), based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow sample. Percentage of Ph+ Cells in Metaphase in bone marrow: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35

  • Pharmacokinetics of Dasatinib (BMS-354825) as Characterized by Population Pharmacokinetics [ Time Frame: Six or more peripheral blood samples were collected at any visit after Day 7, pre-dose and 5 - 8 hours after dose administration. ] [ Designated as safety issue: No ]
    Blood sample collection for pharmacokinetic (PK) analysis that will contribute to PK modeling.

  • Duration of MCyR [ Time Frame: from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death ] [ Designated as safety issue: No ]
    The duration of MCyR will be measured from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death. Subjects who neither progress nor die will be censored on the date of their last cytogenetic assessment.MCyR = a complete and a partial cytogenetic response (CyR), based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow sample. Percentage of Philadelphia-positive (Ph+) Cells in Metaphase in bone marrow: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35

  • Time to CHR [ Time Frame: time from first dose of Dasatinib (BMS-354825) until the first day CHR criteria are met ] [ Designated as safety issue: No ]
    Time to CHR = time from first dose of Dasatinib until the first day CHR criteria are met (provided subjects achieved a cCHR). CHR=all of the following criteria: white blood cell count ≤ upper limit of normal; platelets <450,000/mm³; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils <20%; no extramedullary involvement. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.

  • Duration of CHR [ Time Frame: measured from the first day all criteria were first met for CHR (provided subjects achieved a cCHR), until the date PD is first reported or until death ] [ Designated as safety issue: No ]
    The duration of CHR were measured from the first day all criteria were first met for CHR (provided subjects achieved a cCHR), until the date PD is first reported or until death. Subjects who neither progress nor die were censored on the date of their last hematologic assessment.

  • Progression-Free Survival (PFS) [ Time Frame: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met ] [ Designated as safety issue: No ]
    Progressed disease=achieving a CHR & subsequently no longer meeting criteria consistently over a consecutive 2-week period after starting maximum dose; no CHR after receiving maximum dose & increase in white blood cell count (doubling of count from lowest value to >20,000/mm3 or an increase by >50,000/mm3 on 2 assessments done ≥2 weeks apart); meeting the criteria of accelerated or blastic phase chronic myeloid leukemia at any time; having an MCyR & subsequently no longer meeting the criteria for MCyR after starting maximum dose; or having a >=30% absolute increase in number of Ph+ metaphases.

  • Expression of BCR-ABL Gene Mutations of RNA (mRNA) [ Time Frame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.) ] [ Designated as safety issue: No ]
    Number of participants with positive (>= 2.0 log copies/mg) and negative (<2.0 log copies/mg) expression of mRNA at Baseline and at end of study.

  • Mutational Spectrum of BCR-ABL [ Time Frame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.) ] [ Designated as safety issue: No ]
    Number of participants with a particular BCR-ABL mutation at Baseline and End-of-Study.

  • Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study [ Time Frame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.) ] [ Designated as safety issue: No ]
    Cytogenetic response (CyR) as reflected in the major cytogenetic response was determined by bone marrow (BM) aspirates and are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each BM sample. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), or Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).

  • Hematologic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study [ Time Frame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.) ] [ Designated as safety issue: No ]
    CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils < 20%; no extramedullary involvement. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.


Enrollment: 23
Study Start Date: May 2007
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Dasatinib
tablets, Oral, 100 mg, once daily
Other Names:
  • Sprycel
  • BMS-354825
Experimental: B Drug: dasatinib
tablets, Oral, 50 mg, twice daily
Other Names:
  • Sprycel
  • BMS-354825

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Philadelphia chromosome positive or bcr-abl gene positive Chronic phase Chronic Myelogenous Leukemia (CML) subjects must have primary or acquired resistance to Imatinib mesylate or have intolerance of imatinib mesylate
  • Performance status (general conditions) specified by the Eastern Cooperative Oncology Group: 0-2
  • Men and women, ages 20 to 75
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 3 months after the study in such a manner that the risk of pregnancy is minimized

Exclusion Criteria:

  • Subjects who are eligible and willing to undergo transplantation at pre-study
  • Women who are pregnant or breastfeeding
  • Uncontrolled or significant cardiovascular disease
  • History of significant bleeding disorder unrelated to CML
  • Adequate hepatic function
  • Adequate renal function
  • Medication that increases bleeding risk
  • Medication that changes heart rhythms
  • Subjects who are compulsory detained for legal reasons or treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
  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: NCT00482703

Locations
Japan
Local Institution
Nagoya, Aichi, Japan, 464-8681
Local Institution
Nishinomiya-Shi, Hyogo, Japan, 663-8501
Local Institution
Kagoshima-Shi, Kagoshima, Japan, 890-0064
Local Institution
Isehara-Shi, Kanagawa, Japan, 259-1193
Local Institution
Hamamatsu-Shi, Shizuoka, Japan, 431-3192
Local Institution
Bunkyo-Ku, Tokyo, Japan, 113-8677
Local Institution
Chuo-Ku, Tokyo, Japan, 104-0045
Local Institution
Shibuya-Ku, Tokyo, Japan, 150-8935
Local Institution
Kyoto, Japan
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00482703     History of Changes
Other Study ID Numbers: CA180-138
Study First Received: June 4, 2007
Results First Received: July 23, 2010
Last Updated: November 30, 2010
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Bristol-Myers Squibb:
Imatinib resistant or intolerant chronic phase CML

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Abnormal Karyotype
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014