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 (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01077622
First received: February 25, 2010
Last updated: October 31, 2013
Last verified: February 2012
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
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
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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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
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 ]

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 ]

3.  Secondary:   Progression-free Survival (PFS) as Assessed by a SERC   [ Time Frame: Up to Week 48 ]

4.  Secondary:   Duration of Response as Assessed by a SERC   [ Time Frame: Up to Week 48 ]

5.  Secondary:   Overall Survival   [ Time Frame: Up to Week 48 ]

6.  Secondary:   Time to Response as Assessed by a SERC   [ Time Frame: Up to Week 48 ]

7.  Secondary:   Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy as Assessed by a SERC   [ Time Frame: Up to Week 48 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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

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

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

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

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 ]

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 ]

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 ]

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 ]

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

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

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

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

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

Measure Type Other Pre-specified
Measure Title Serum Hemolytic Complement Titer at Weeks 36 and 48: CH50
Measure Description The CH50 is the serum complement to lyse 50% of sensitized red blood cells; it's is a marker of complement activation. A high CH50 level suggests evidence for complement activation, whereas a low CH50 level suggests lack of complement activation.
Time Frame Weeks 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  
Serum Hemolytic Complement Titer at Weeks 36 and 48: CH50  
[units: Kilo units per liter (KU/L)]
Mean ± Standard Deviation
 
Week 36, n=8     45.14  ± 13.643  
Week 48, n=7     53.70  ± 11.818  

No statistical analysis provided for Serum Hemolytic Complement Titer at Weeks 36 and 48: CH50




  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: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided


Responsible Party: GlaxoSmithKline
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: October 31, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare