Study of Dasatinib (BMS-354825) in Patients With Accelerated Phase Chronic Myeloid Leukemia

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00101647
First received: January 12, 2005
Last updated: April 13, 2011
Last verified: April 2011
Results First Received: December 22, 2009  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Chronic Myelogenous Leukemia
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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
197 participants were enrolled into the study; 23 participants were not treated (3 participants died, 13 participants no longer met study criteria, 3 participants switched into other studies, 2 participants had adverse events, 1 participant excluded for administrative reasons, and 1 participant withdrew consent).

Reporting Groups
  Description
Imatinib-intolerant Defined as either: i) toxicity that was considered at least possibly related to imatinib ≤ 400 mg/day that led to a discontinuation of imatinib therapy; ii) ability to tolerate only < 400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses, was not considered imatinib-tolerant.
Imatinib-resistant Defined as any of the following: i) initial diagnosis of chronic phase of chronic myeloid leukemia (CML) that progressed to accelerated phase while on treatment with imatinib ≥ 400 mg/day (primary or acquired resistance); ii) initial diagnosis of accelerated phase CML and failure to achieve a hematologic response after ≥ 4 weeks (or ≥ 2 weeks for subjects showing rapid disease progression) of imatinib ≥ 600 mg/day; the required prior imatinib dose was 400 to < 600 mg/day if the subject was intolerant to ≥ 600 mg/day (primary resistance); iii) initial diagnosis of accelerated or blast phase CML that progressed to accelerated phase CML following an initial hematologic response to imatinib ≥ 600 mg/day (acquired resistance). The required prior imatinib dose was 400 to < 600 mg/day if the subject was intolerant of ≥ 600 mg/day.

Participant Flow:   Overall Study
    Imatinib-intolerant     Imatinib-resistant  
STARTED     13 [1]   161 [1]
COMPLETED     13     161  
NOT COMPLETED     0     0  
[1] Randomized



  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.
No text entered.

Reporting Groups
  Description
Imatinib-intolerant Defined as either: i) toxicity that was considered at least possibly related to imatinib ≤ 400 mg/day that led to a discontinuation of imatinib therapy; ii) ability to tolerate only < 400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses, was not considered imatinib-tolerant.
Imatinib-resistant Defined as any of the following: i) initial diagnosis of chronic phase of chronic myeloid leukemia (CML) that progressed to accelerated phase while on treatment with imatinib ≥ 400 mg/day (primary or acquired resistance); ii) initial diagnosis of accelerated phase CML and failure to achieve a hematologic response after ≥ 4 weeks (or ≥ 2 weeks for subjects showing rapid disease progression) of imatinib ≥ 600 mg/day; the required prior imatinib dose was 400 to < 600 mg/day if the subject was intolerant to ≥ 600 mg/day (primary resistance); iii) initial diagnosis of accelerated or blast phase CML that progressed to accelerated phase CML following an initial hematologic response to imatinib ≥ 600 mg/day (acquired resistance). The required prior imatinib dose was 400 to < 600 mg/day if the subject was intolerant of ≥ 600 mg/day.
Total Total of all reporting groups

Baseline Measures
    Imatinib-intolerant     Imatinib-resistant     Total  
Number of Participants  
[units: participants]
  13     161     174  
Age, Customized  
[units: participants]
     
21 to 45 years     2     41     43  
46 to 65 years     6     87     93  
66 to 75 years     4     25     29  
>75 years     1     8     9  
Age  
[units: years]
Mean ± Standard Deviation
  58.4  ± 14.2     54.5  ± 13.7     54.8  ± 13.7  
Gender  
[units: participants]
     
Female     9     69     78  
Male     4     92     96  
Race/Ethnicity, Customized  
[units: participants]
     
Asian     1     23     24  
Black or African American     1     8     9  
White     11     127     138  
Other     0     3     3  
Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) [1]
[units: units on a scale]
     
score=0 fully active     6     73     79  
score=1 physically strenuous activity restricted     4     67     71  
score=2 capable of all selfcare, unable to work     3     21     24  
score=3 limited selfcare, bed/chair confined >50%     0     0     0  
score=4 completely disabled, bed/chair confined     0     0     0  
score=5 dead     0     0     0  
Functional Assessment of Cancer Therapy-General (FACT-G) [2]
[units: units on a scale]
Mean ± Standard Deviation
     
Total FACT-G     81.9  ± 14.4     75.3  ± 18.0     75.8  ± 17.8  
Physical Well Being     22.3  ± 5.2     19.0  ± 7.1     19.2  ± 7.0  
Social/Family Well-Being     22.8  ± 5.1     22.7  ± 4.8     22.7  ± 4.8  
Emotional Well-Being     17.7  ± 4.8     16.7  ± 4.9     16.8  ± 4.9  
Functional Well-Being     19.2  ± 6.9     16.9  ± 6.7     17.1  ± 6.8  
[1] ECOG scale is a 6-item scale to assess disease progression, daily functioning, and appropriate treatment and prognosis. Scale 0-5, with 0=fully active, able to carry on all pre-disease performance without restriction, and 5=death
[2] FACT-G=27 questions in 4 domains: physical, social/family, emotional, & functional well-being (PWB, SWB, EWB, FWB). Total score=0 to 108; higher score=better health-related quality of life. 12 participants in the Imatinib-Intolerant group had baseline measurements; 130 participants in the Imatinib-Resistant group had baseline measurements for Total FACT-G scores; 134 for PWB; 133 for FWB and SWB; 131 for EWB.



  Outcome Measures
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1.  Primary:   Major and Overall Hematologic Response (MaHR and OHR)   [ Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment ]

2.  Secondary:   Percentage of Participants Who Achieved MaHR and Did Not Progress at 12 Months (Based on the Kaplan-Meier Estimate of the Duration of Response)   [ Time Frame: 12 months ]

3.  Secondary:   Percentage of Participants Who Achieved MaHR and Did Not Progress at 24 Months in the Imatinib-Resistant Group (Based on the Kaplan-Meier Estimate of the Duration of Response)   [ Time Frame: 24 months ]

4.  Secondary:   Percentage of Participants Who Achieved OHR and Did Not Progress at 12 Months and 24 Months   [ Time Frame: 12 months, 24 months ]

5.  Secondary:   Median Time in Days From First Dosing Date to Date of MaHR   [ Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment ]

6.  Secondary:   Time to OHR   [ Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment ]

7.  Secondary:   Best Cytogenetic Response   [ Time Frame: Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment ]

8.  Secondary:   Best Confirmed Hematologic Response   [ Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment ]

9.  Secondary:   Number of Participants Who Achieved a Major Molecular Response (MMR) During Treatment Period   [ Time Frame: Baseline, every 12 weeks throughout study (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria). ]

10.  Secondary:   MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations   [ Time Frame: Baseline, at time of disease progression. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria). ]

11.  Secondary:   Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)   [ Time Frame: Baseline, every 2 weeks for the first 3 cycles, following every 4-week cycle, and once at follow-up.(treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria). ]

12.  Secondary:   Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation   [ Time Frame: Continuous from pretreatment through each 4-week cycle and at follow-up. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria). ]

13.  Secondary:   Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax)   [ Time Frame: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours. ]

14.  Secondary:   Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 Hours (AUC[0-T])   [ Time Frame: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours. ]

15.  Secondary:   Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax)   [ Time Frame: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours. ]

16.  Secondary:   Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF)   [ Time Frame: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours. ]

17.  Secondary:   Population PK of Dasatinib   [ Time Frame: Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose. ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
No text entered.  


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


Publications:

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00101647     History of Changes
Obsolete Identifiers: NCT00108693
Other Study ID Numbers: CA180-005
Study First Received: January 12, 2005
Results First Received: December 22, 2009
Last Updated: April 13, 2011
Health Authority: United States: Food and Drug Administration