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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 25, 2016
Last verified: July 2016
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
Overall Participants Analyzed 
[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
  Show All Outcome Measures

1.  Primary:   Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up   [ Time Frame: 6 months ]

2.  Secondary:   Percent of Participants With MCyR At or Prior to 24 Months Follow-Up   [ Time Frame: 24 months ]

3.  Secondary:   Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up   [ Time Frame: 6 months, 24 months ]

4.  Secondary:   Time to MCyR in Participants With MCyR at 6 Months Follow-Up   [ Time Frame: 6 months ]

5.  Secondary:   Time to CHR in Participants With CHR at 6 Months Follow-Up   [ Time Frame: 6 months ]

6.  Secondary:   Time to MCyR in Participants With MCyR at 24 Months Follow-Up   [ Time Frame: 24 months ]

7.  Secondary:   Time to CHR in Participants With CHR At 24 Months Follow-Up   [ Time Frame: 24 months ]

8.  Secondary:   Number of Participants With MCyR Whose Disease Progressed by 24 Months   [ Time Frame: 24 months ]

9.  Secondary:   Number of Participants With CHR Whose Disease Progressed by 24 Months   [ Time Frame: 24 months ]

10.  Secondary:   Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants   [ Time Frame: Baseline up to 24 months ]

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

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

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

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

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: 24, 36, 48, 60, 72, and 84 months ]

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

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) at 6 Months Follow-Up   [ Time Frame: 6 months ]

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) at 24 Months Follow-Up   [ Time Frame: 24 months ]

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: 24, 36, 48, 60, 72, and 84 months ]

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

21.  Secondary:   Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up   [ Time Frame: Baseline to 30 days post last dose, up to 24 months ]

22.  Secondary:   Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up   [ Time Frame: Baseline to 30 days post last dose, up to 7 years (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 by ClinicalTrials.gov Identifier (NCT Number):

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 25, 2016
Health Authority: United States: Food and Drug Administration