Chronic Myelogenous Leukemia (CML) - Follow on: Study of BMS-354825 in Subjects With CML

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00123474
First received: July 21, 2005
Last updated: July 29, 2015
Last verified: July 2015
Results First Received: June 29, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Myeloid Leukemia, Chronic, Chronic-Phase
Intervention: Drug: dasatinib

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study initiated July 2005 and completed July 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
724 participants were enrolled, 670 were randomized, and 662 were treated with study drug. Reasons for non-randomization: 38 no longer met criteria, 8 other reasons, 7 withdrew consent, and 1 death.

Reporting Groups
  Description
Dasatinib 100 mg QD Participants received 100 mg once a day (QD) until progression of disease, development of intolerable toxicity, or the participant’s decision to withdraw.
Dasatinib 140 mg QD Participants received 140 mg QD until progression of disease, development of intolerable toxicity, or the participant’s decision to withdraw.
Dasatinib 50 mg BID Participants received 50 mg twice a day (BID) until progression of disease, development of intolerable toxicity, or the participant’s decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.
Dasatinib 70 mg BID Participants received 70 mg BID until progression of disease, development of intolerable toxicity, or the participant’s decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.

Participant Flow for 2 periods

Period 1:   Randomized to Treatment
    Dasatinib 100 mg QD     Dasatinib 140 mg QD     Dasatinib 50 mg BID     Dasatinib 70 mg BID  
STARTED     167     167     168     168  
COMPLETED     166     163     166     167  
NOT COMPLETED     1     4     2     1  
Randomized, never treated                 1                 4                 2                 1  

Period 2:   As Treated at Study Closure
    Dasatinib 100 mg QD     Dasatinib 140 mg QD     Dasatinib 50 mg BID     Dasatinib 70 mg BID  
STARTED     165 [1]   163     167     167  
COMPLETED     0     0     0 [2]   0  
NOT COMPLETED     165     163     167     167  
not reported when site closed                 1                 0                 1                 0  
Adverse Event                 10                 4                 10                 8  
Disease Progression                 35                 42                 29                 27  
Investigator Request                 12                 6                 7                 5  
non-specified                 54                 47                 57                 60  
Study Drug Toxicity                 39                 45                 45                 51  
Withdrawal by Subject                 14                 19                 18                 16  
[1] Randomized to 50 mg BID but received 100 mg QD.
[2] Randomized to 100 mg QD but received 50 mg BID.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized to a treatment arm are summarized.

Reporting Groups
  Description
Dasatinib 100 mg QD Participants received 100 mg once a day (QD) until progression of disease, development of intolerable toxicity, or the participant’s decision to withdraw.
Dasatinib 140 mg QD Participants received 140 mg QD until progression of disease, development of intolerable toxicity, or the participant’s decision to withdraw.
Dasatinib 50 mg BID Participants received 50 mg twice a day (BID) until progression of disease, development of intolerable toxicity, or the participant’s decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.
Dasatinib 70 mg BID Participants received 70 mg BID until progression of disease, development of intolerable toxicity, or the participant’s decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.
Total Total of all reporting groups

Baseline Measures
    Dasatinib 100 mg QD     Dasatinib 140 mg QD     Dasatinib 50 mg BID     Dasatinib 70 mg BID     Total  
Number of Participants  
[units: participants]
  167     167     168     168     670  
Age, Customized  
[units: participants]
         
Less than, equal to (<=) 65 years     121     128     130     125     504  
Greater than (>) 65 years     46     39     38     43     166  
Gender  
[units: participants]
         
Female     83     97     83     91     354  
Male     84     70     85     77     316  
Imatinib Status [1]
[units: participants]
         
Primary Resistance to Imatinib     75     78     88     81     322  
Acquired Resistance to Imatinib     49     45     36     45     175  
Intolerant to Imatinib     43     44     44     42     173  
[1] Primary Resistance: no decrease in white blood cell (WBC) count after ≥ 4 weeks imatinib or not achieved a complete hematologic response (CHR) after 3 months, a major cytogenetic response (MCyR) after 6 months, or a complete cytogenetic response (CCyR) after 12 months. Acquired resistance: achieved MCyR and no longer met the criteria for MCyR. Intolerance: Grade ≥ 3 toxicity considered at least possibly related to imatinib at a dose of ≤ 400 mg/day which led to discontinuation of therapy; tolerated the dose of 400 mg but did not achieve a CCyR and subsequently did not tolerate doses ≥ 600 mg.



  Outcome Measures
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1.  Primary:   Percent of Participants With Major Cytogenetic Response (MCyR) After at Least 6 Months Follow-Up   [ Time Frame: Baseline and after at least 6 months follow-up ]

2.  Secondary:   Percent of Participants With MCyR At or Prior to 24 Months Follow-Up   [ Time Frame: Baseline and after at least 24 months follow-up ]

3.  Secondary:   Percent of Participants With Complete Hematologic Response (CHR) After at Least 6 and 24 Months Follow-Up   [ Time Frame: Baseline and after at least 6 and 24 months follow-up ]

4.  Secondary:   Time to MCyR in Participants With MCyR After At Least 6 Months Follow-Up   [ Time Frame: Baseline and after at least 6 months follow-up ]

5.  Secondary:   Time to CHR in Participants With CHR After at Least 6 Months Follow-Up   [ Time Frame: Baseline and after at least 6 months follow-up ]

6.  Secondary:   Time to MCyR in Participants With MCyR After at Least 24 Months Follow-Up   [ Time Frame: Baseline and after at least 24 months follow-up ]

7.  Secondary:   Time to CHR in Participants With CHR After at Least 24 Months Follow-Up   [ Time Frame: Baseline and after at least 24 months follow-up ]

8.  Secondary:   Number of Participants With MCyR Whose Disease Progressed   [ Time Frame: Baseline and after at least 24 months follow-up ]

9.  Secondary:   Number of Participants With CHR Whose Disease Progressed   [ Time Frame: Baseline and after at least 24 months follow-up ]

10.  Secondary:   Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants   [ Time Frame: Baseline to Year 2 ]

11.  Secondary:   Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) After at Least 24, 36, 48, 60, 72, and 84 Months Follow-Up   [ Time Frame: Baseline and after 84 months follow-up ]

12.  Secondary:   Percent of Imatinib-Resistant Participants With Overall Survival (OS) After at Least 24, 36, 48, 60, 72, and 84 Months Follow-Up   [ Time Frame: Baseline and after 84 months follow-up ]

13.  Secondary:   Percent of Participants Intolerant to Imatinib With MCyR After at Least 6 Months and After at Least 24 Months Follow-Up, by QD and BID Schedules and by Total Daily Dose   [ Time Frame: Baseline and after at Least 6 Months and 24 Months Follow-Up ]

14.  Secondary:   Percent of Participants Intolerant to Imatinib With CHR After at Least 6 Months and After at Least 24 Months Follow-Up   [ Time Frame: Baseline and after at Least 6 Months and 24 Months Follow Up ]

15.  Secondary:   Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up   [ Time Frame: Baseline and after 84 months follow-up ]

16.  Secondary:   Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up   [ Time Frame: Baseline and after 84 months follow-up ]

17.  Secondary:   Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) After at Least 6 Months Follow-Up   [ Time Frame: Baseline and after at least 6 months follow-up ]

18.  Secondary:   Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) After at Least 24 Months Follow-Up   [ Time Frame: Baseline and after at least 24 months follow-up ]

19.  Secondary:   Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants   [ Time Frame: Baseline and after 84 Months Follow-up ]

20.  Secondary:   Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants   [ Time Frame: Baseline up to 84 Months Follow-up ]

21.  Secondary:   Baseline and After 2 Years Follow-Up: Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation   [ Time Frame: Baseline and after 2 Years Follow-Up ]

22.  Secondary:   Baseline and After 7 Years Follow-Up and Study Closure: Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation   [ Time Frame: Baseline to 30 days post last dose;7 years follow up; study closure July 2014 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


Publications:
Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00123474     History of Changes
Other Study ID Numbers: CA180-034
Study First Received: July 21, 2005
Results First Received: June 29, 2015
Last Updated: July 29, 2015
Health Authority: United States: Food and Drug Administration