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A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01077622
First received: February 25, 2010
Last updated: February 2, 2012
Last verified: February 2012
History of Changes
Results First Received: December 21, 2011  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Leukaemia, Lymphocytic, Chronic
Intervention: Drug: ofatumumab 100 mg, 1000 mg / vial

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Ofatumumab Participants received intravenous ofatumumab at an initial dose of 300 milligrams (mg). One week after the initial dose, participants received 7 infusions of 2000 mg at weekly intervals. Five weeks after the last 2000 mg infusion, participants received 4 infusions of 2000 mg at 4-week intervals.

Participant Flow:   Overall Study
    Ofatumumab  
STARTED     10  
COMPLETED     7  
NOT COMPLETED     3  
Physician Decision                 2  
Withdrawal by Subject                 1  



  Baseline Characteristics
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Reporting Groups
  Description
Ofatumumab Participants received intravenous ofatumumab at an initial dose of 300 milligrams (mg). One week after the initial dose, participants received 7 infusions of 2000 mg at weekly intervals. Five weeks after the last 2000 mg infusion, participants received 4 infusions of 2000 mg at 4-week intervals.

Baseline Measures
    Ofatumumab  
Number of Participants  
[units: participants]
 		  10  
Age  
[units: Years]
Mean ± Standard Deviation 		  66.3  ± 5.87  
Gender  
[units: Participants]
 		 
Female     3  
Male     7  
Race/Ethnicity, Customized  
[units: participants]
 		 
Asian - East Asian Heritage     1  
Asian – Japanese Heritage     9  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With a Dose-limiting Toxicity (DLT)   [ Time Frame: Up to Week 8 ]
  Show Outcome Measure 1

2.  Primary:   Percentage of Participants (Par.) With Objective Response (OR), Defined as Complete Remission (CR), CR Incomplete (CRi), Partial Remission (PR), and Nodular PR (nPR) as Assessed by a Safety and Evaluation Review Committee (SERC) and the Investigator   [ Time Frame: Up to Week 48 ]
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3.  Secondary:   Progression-free Survival (PFS) as Assessed by a SERC   [ Time Frame: Up to Week 48 ]
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4.  Secondary:   Duration of Response as Assessed by a SERC   [ Time Frame: Up to Week 48 ]
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5.  Secondary:   Overall Survival   [ Time Frame: Up to Week 48 ]
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6.  Secondary:   Time to Response as Assessed by a SERC   [ Time Frame: Up to Week 48 ]
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7.  Secondary:   Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy as Assessed by a SERC   [ Time Frame: Up to Week 48 ]
  Show Outcome Measure 7

8.  Secondary:   Mean Laboratory Data for Hemoglobin at the Indicated Weeks as Assessed by the Investigator   [ Time Frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 8

9.  Secondary:   Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by the Investigator   [ Time Frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 9

10.  Secondary:   Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator   [ Time Frame: Weeks 8, 16, 24, 36, and 48 ]
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Measure Type Secondary
Measure Title Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator
Measure Description Bone marrow (BM) aspiration was performed, and the bone marrow smears were prepared for the assessment of lymphocytes in the BM.
Time Frame Weeks 8, 16, 24, 36, and 48  
Safety Issue No  

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 Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed.

Reporting Groups
  Description
Ofatumumab Participants received intravenous ofatumumab at an initial dose of 300 milligrams (mg). One week after the initial dose, participants received 7 infusions of 2000 mg at weekly intervals. Five weeks after the last 2000 mg infusion, participants received 4 infusions of 2000 mg at 4-week intervals.

Measured Values
    Ofatumumab  
Number of Participants Analyzed  
[units: participants]
 		  8  
Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator  
[units: Percentage of lymphocytes in the BM]
Mean ± Standard Deviation 		 
Week 8, n=8     57.90  ± 23.492  
Week 16, n=5     38.04  ± 14.647  
Week 24, n=7     36.96  ± 14.961  
Week 36, n=6     30.00  ± 17.030  
Week 48, n=5     23.26  ± 9.651  

No statistical analysis provided for Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator



11.  Secondary:   Mean Laboratory Data for Total Neutrophils (Total Absolute Neutrophil Count [ANC]) at the Indicated Weeks as Assessed by the Investigator   [ Time Frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 11

12.  Secondary:   Mean Laboratory Data for Platelet Count at the Indicated Weeks as Assessed by the Investigator   [ Time Frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 12

13.  Secondary:   Percentage of Bone Marrow Infiltration at the Indicated Weeks as Assessed by a SERC   [ Time Frame: Weeks 8, 16, 24, 36, and 48 ]
  Show Outcome Measure 13

14.  Secondary:   Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by a SERC   [ Time Frame: Weeks 8, 16, 24, 36, and 48 ]
  Show Outcome Measure 14

15.  Secondary:   Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by a SERC   [ Time Frame: Weeks 8, 16, 24, 36, and 48 ]
  Show Outcome Measure 15

16.  Secondary:   Mean Laboratory Data for Total Neutrophils (Total ANC) at the Indicated Weeks as Assessed by a SERC   [ Time Frame: Weeks 8, 16, 24, 36, and 48 ]
  Show Outcome Measure 16

17.  Secondary:   Number of Peripheral Blood Cluster of Differentiation (CD) CD19+ CD20+ Cells   [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 17

18.  Secondary:   Number of Peripheral Blood CD20+ CD23+ Cells   [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ]
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19.  Secondary:   Number of Peripheral Blood CD19+ CD23+ Cells   [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ]
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20.  Secondary:   Number of Peripheral Blood CD19+ CD5+ Cells   [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ]
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21.  Secondary:   Number of Peripheral Blood CD20+ CD5+ Cells   [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ]
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22.  Secondary:   Number of Peripheral Blood CD23+ CD5+ Cells   [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 22

23.  Secondary:   Ratio of Immunoglobulin (Ig) Kappa/Ig Lambda   [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 23

24.  Secondary:   Number of Participants With the Indicated Shift From Baseline (BL) in Night Sweats at the Indicated Weeks   [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 24

25.  Secondary:   Number of Participants With the Indicated Shift From Baseline (BL) in Weight Loss at the Indicated Weeks   [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
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26.  Secondary:   Number of Participants With the Indicated Shift From Baseline (BL) in Fever at the Indicated Weeks   [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
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27.  Secondary:   Number of Participants With the Indicated Shift From Baseline (BL) in Extreme Fatigue at the Indicated Weeks   [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
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28.  Secondary:   Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Weeks 8, 24, and 48   [ Time Frame: Baseline and Weeks 8, 24, and 48 ]
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29.  Secondary:   Number of Participants Who Tested Positive/Negative for Human Anti-human Antibodies (HAHA) at Screening and at Weeks 24 and 48   [ Time Frame: Screening; Weeks 24 and 48 ]
  Show Outcome Measure 29

30.  Secondary:   Number of Participants With a Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ]
  Show Outcome Measure 30

31.  Secondary:   Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 31

32.  Secondary:   Minimum Plasma Concentration (Cmin) of Ofatumumab   [ Time Frame: Weeks 7 and 24 ]
  Show Outcome Measure 32

33.  Secondary:   Time to Reach Cmax (Tmax) Following Ofatumumab Administration   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 33

34.  Secondary:   Half-life (t1/2) of Ofatumumab   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 34

35.  Secondary:   Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for Ofatumumab   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 35

36.  Secondary:   Area Under the Plasma Concentration-time Curve From Time Zero to 168 hr (AUC[0-168]) for Ofatumumab at Week 7   [ Time Frame: Week 7 ]
  Show Outcome Measure 36

37.  Secondary:   Area Under the Plasma Concentration-time Curve From Time Zero to 672 hr (AUC[0-672]) for Ofatumumab at Week 24   [ Time Frame: Week 24 ]
  Show Outcome Measure 37

38.  Secondary:   Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 38

39.  Secondary:   Clearance (CL) of Ofatumumab From Plasma   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 39

40.  Secondary:   Volume of Distribution (Vz) During the Terminal Phase for Ofatumumab   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 40

41.  Secondary:   Volume of Distribution at Steady State (Vss) for Ofatumumab   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 41

42.  Secondary:   Mean Residence Time (MRTinf) of Ofatumumab   [ Time Frame: Day 1; Weeks 7 and 24 ]
  Show Outcome Measure 42

43.  Other Pre-specified:   Serum Hemolytic Complement Titer at Weeks 36 and 48: CH50   [ Time Frame: Weeks 36 and 48 ]
  Show Outcome Measure 43


  Serious Adverse Events
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  Other Adverse Events
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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.


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
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Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided


Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01077622     History of Changes
Other Study ID Numbers: 112758
Study First Received: February 25, 2010
Results First Received: December 21, 2011
Last Updated: February 2, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare