Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML

This study has been completed.
Sponsor:
Collaborators:
Cephalon
ChemGenex Pharmaceuticals
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT00462943
First received: April 17, 2007
Last updated: June 27, 2014
Last verified: June 2014
Results First Received: May 5, 2014  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Chronic Myeloid Leukemia
Intervention: Drug: Omacetaxine mepesuccinate

  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
CML: Chronic Phase Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 24 months.
CML: Accelerated Phase Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 24 months.
CML: Blast Phase Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 24 months.

Participant Flow:   Overall Study
    CML: Chronic Phase     CML: Accelerated Phase     CML: Blast Phase  
STARTED     46     31     23  
COMPLETED     1     1     0  
NOT COMPLETED     45     30     23  
Failure to achieve a response                 5                 5                 1  
Adverse Event                 6                 4                 1  
Protocol Violation                 1                 0                 0  
Request of Patient, PI, Sponsor or RA                 8                 2                 4  
Disease Progression                 15                 15                 9  
Death                 5                 2                 7  
Stem Cell Transplant                 1                 1                 0  
Bone Marrow Transplant                 1                 0                 0  
Required Lymphocyte Infusion                 1                 0                 0  
Transplant - not specified                 1                 0                 1  
Physician Decision                 1                 0                 0  
Withdrawal by Subject                 0                 1                 0  



  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.
Intent to Treat Population: all participants who provided written informed consent and received at least 1 dose of study drug constitute the ITT population.

Reporting Groups
  Description
CML: Chronic Phase Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 24 months.
CML: Accelerated Phase Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 24 months.
CML: Blast Phase Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 24 months.
Total Total of all reporting groups

Baseline Measures
    CML: Chronic Phase     CML: Accelerated Phase     CML: Blast Phase     Total  
Number of Participants  
[units: participants]
  46     31     23     100  
Age  
[units: years]
Median ( Full Range )
  58  
  ( 20 to 78 )  
  56  
  ( 23 to 71 )  
  57  
  ( 30 to 68 )  
  57  
  ( 20 to 78 )  
Gender  
[units: participants]
       
Female     20     12     9     41  
Male     26     19     14     59  
Race/Ethnicity, Customized  
[units: participants]
       
Caucasian     31     17     12     60  
Black     2     4     5     11  
Hispanic     3     2     1     6  
Asian     7     7     4     18  
Other     3     1     1     5  
Height  
[units: centimeter]
Median ( Full Range )
  167.7  
  ( 155.0 to 188.0 )  
  167.5  
  ( 148.0 to 195.0 )  
  171.0  
  ( 149.9 to 191.0 )  
  167.6  
  ( 148.0 to 195.0 )  
Weight  
[units: kilograms]
Median ( Full Range )
  79.5  
  ( 40.0 to 138.0 )  
  67.4  
  ( 36.5 to 111.8 )  
  74.0  
  ( 41.0 to 136.4 )  
  74.2  
  ( 36.5 to 138.0 )  
Body Surface Area (BSA)  
[units: meters^2]
Median ( Full Range )
  1.9  
  ( 1.3 to 2.5 )  
  1.7  
  ( 1.4 to 2.2 )  
  1.9  
  ( 1.4 to 2.5 )  
  1.9  
  ( 1.3 to 2.5 )  
New York Heart Association (NYHA) Classification [1]
[units: participants]
       
Class I     44     29     23     96  
Class II     2     0     0     2  
Class III     0     0     0     0  
Class IV     0     0     0     0  
Not available     0     2     0     2  
Eastern Cooperative Oncology Group Performance Status [2]
[units: participants]
       
Grade 0     27     7     6     40  
Grade 1     17     19     11     47  
Grade 2     2     5     5     12  
Grade 3     0     0     1     1  
Time from Initial Chronic Myeloid Leukemia (CML) Diagnosis  
[units: months]
Median ( Full Range )
  74.4  
  ( 7.9 to 221.0 )  
  83.5  
  ( 20.3 to 197.1 )  
  68.7  
  ( 6.6 to 195.5 )  
  74.0  
  ( 6.6 to 221.0 )  
[1]
  • Class I: Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.
  • Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.
  • Class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20–100 m). Comfortable only at rest.
  • Class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bed-bound patients.
[2]
  • Grade 0: Fully active, able to carry on all pre-disease activities without restriction;
  • Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature;
  • Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours;
  • Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours;
  • Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or chair.



  Outcome Measures
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1.  Primary:   Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population   [ Time Frame: Day 1 up to 6 months ]

2.  Primary:   Percentage of Participants Achieving a Major Cytogenetic Response by Subpopulation and Total Population   [ Time Frame: Day 1 up to 9 months ]

3.  Primary:   Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Subpopulation and Total   [ Time Frame: up to 4 years ]

4.  Secondary:   Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+)   [ Time Frame: Day 1 up to Month 9 ]

5.  Secondary:   Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS   [ Time Frame: Day 1 up to Month 6 ]

6.  Secondary:   Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL   [ Time Frame: Day 1 up to Month 6 ]

7.  Secondary:   Percentage of Participants in Each Hematologic Response Category   [ Time Frame: Day 1 up to Month 6 ]

8.  Secondary:   Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response   [ Time Frame: Day 1 up to Month 9 ]

9.  Secondary:   Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL   [ Time Frame: Day 1 up to Month 9 ]

10.  Secondary:   Number of Treatment Cycles Needed to Achieve Best Hematologic Response   [ Time Frame: Day 1 up to Month 6 ]

11.  Secondary:   Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response   [ Time Frame: Day 1 up to Month 9 ]

12.  Secondary:   Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response   [ Time Frame: Day 1 up to Month 6 ]

13.  Secondary:   Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response   [ Time Frame: Day 1 up to Month 9 ]

14.  Secondary:   Kaplan-Meier Estimates for Duration of Best Hematologic Response   [ Time Frame: up to four years ]

15.  Secondary:   Kaplan-Meier Estimates for Duration of Best Cytogenetic Response   [ Time Frame: up to four years ]

16.  Secondary:   Kaplan-Meier Estimates for Time to Disease Progression   [ Time Frame: up to 4 years ]

17.  Secondary:   Kaplan-Meier Estimates for Overall Survival   [ Time Frame: up to 4 years ]


  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: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
phone: 215-591-3000
e-mail: ustevatrials@tevapharm.com


No publications provided by Teva Pharmaceutical Industries

Publications automatically indexed to this study:

Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT00462943     History of Changes
Other Study ID Numbers: CGX-635-CML-203, 2007-001286-15
Study First Received: April 17, 2007
Results First Received: May 5, 2014
Last Updated: June 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
European Union: European Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India
Singapore: Health Sciences Authority