Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00333840
First received: June 2, 2006
Last updated: August 7, 2013
Last verified: August 2013
Results First Received: March 15, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Chronic Myelogenous Leukemia
Interventions: Drug: imatinib mesilate
Drug: interferon-alpha (INF-a)
Drug: cytarabine (ARA-C)

  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
No text entered.

Reporting Groups
  Description
Imatinib (STI571) In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
IFN-a + Ara-C In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
Imatinib to IFN-a + Ara-C In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m^2/day (max 40 mg) SC injections for 10 days every month.
IFN-a + Ara-C to Imatinib In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571) 400 mg orally once daily in the morning.

Participant Flow for 2 periods

Period 1:   First-line Treatment Period
    Imatinib (STI571)     IFN-a + Ara-C     Imatinib to IFN-a + Ara-C     IFN-a + Ara-C to Imatinib  
STARTED     553     553     0     0  
Safety Population; Received Study Drug     551     533     0     0  
COMPLETED     267     7     0     0  
NOT COMPLETED     286     546     0     0  
Adverse Event                 38                 37                 0                 0  
Abnormal laboratory values                 3                 1                 0                 0  
Abnormal procedure                 2                 0                 0                 0  
Unsatisfactory therapeutic effect                 88                 29                 0                 0  
No longer required study drug                 21                 8                 0                 0  
Protocol Violation                 17                 17                 0                 0  
Subject withdrew consent                 57                 77                 0                 0  
Lost to Follow-up                 15                 6                 0                 0  
Administrative problems                 12                 6                 0                 0  
Death                 19                 2                 0                 0  
Crossed over to other treatment arm                 14                 363                 0                 0  

Period 2:   Second-line Treatment Period
    Imatinib (STI571)     IFN-a + Ara-C     Imatinib to IFN-a + Ara-C     IFN-a + Ara-C to Imatinib  
STARTED     0     0     14     363  
COMPLETED     0     0     0     175  
NOT COMPLETED     0     0     14     188  
Adverse Event                 0                 0                 3                 34  
Abnormal Laboratory Values                 0                 0                 0                 3  
Abnormal procedure                 0                 0                 0                 1  
Unsatisfactory therapeutic effect                 0                 0                 9                 70  
No longer required study drug                 0                 0                 1                 14  
Protocol Violation                 0                 0                 1                 10  
Subject withdrew consent                 0                 0                 0                 34  
Lost to Follow-up                 0                 0                 0                 6  
Administrative problems                 0                 0                 0                 7  
Death                 0                 0                 0                 9  



  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 (STI571) In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
IFN-a + Ara-C In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (CSI151). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
Total Total of all reporting groups

Baseline Measures
    Imatinib (STI571)     IFN-a + Ara-C     Total  
Number of Participants  
[units: participants]
  553     553     1106  
Age  
[units: years]
Median ( Full Range )
  50.0  
  ( 18 to 70 )  
  51.0  
  ( 18 to 70 )  
  51.0  
  ( 18 to 70 )  
Gender  
[units: participants]
     
Female     211     243     454  
Male     342     310     652  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)   [ Time Frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months ]

2.  Secondary:   Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)   [ Time Frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months ]

3.  Secondary:   Percentage of Participants With Event Free Survival Events (All Randomized Participants)   [ Time Frame: 144 months ]

4.  Secondary:   Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)   [ Time Frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months ]

5.  Secondary:   Percentage of Participants With Best Cytogenetic Response (First-line Treatment)   [ Time Frame: 144 months ]

6.  Secondary:   Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)   [ Time Frame: 144 months ]

7.  Secondary:   Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment)   [ Time Frame: 144 months ]

8.  Secondary:   Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment)   [ Time Frame: 144 months ]

9.  Secondary:   Percentage of Participants With Major Molecular Response (First-line Treatment)   [ Time Frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months ]

10.  Secondary:   Percentage of Participants With Major Molecular Response (Second-line Treatment)   [ Time Frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months ]


  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: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00333840     History of Changes
Other Study ID Numbers: CSTI571A 0106
Study First Received: June 2, 2006
Results First Received: March 15, 2013
Last Updated: August 7, 2013
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration