We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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:
ClinicalTrials.gov Identifier:
NCT01077622
First Posted: March 1, 2010
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
Results First Submitted: December 21, 2011  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Leukaemia, Lymphocytic, Chronic
Intervention: Drug: ofatumumab 100 mg, 1000 mg / vial

  Participant Flow
  Hide Participant Flow

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
  Hide Baseline Characteristics

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 
Overall Participants Analyzed 
[Units: Participants]
 10 
Age 
[Units: Years]
Mean (Standard Deviation)
 66.3  (5.87) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      3  30.0% 
Male      7  70.0% 
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 ]
  Hide Outcome Measure 42

Measure Type Secondary
Measure Title Mean Residence Time (MRTinf) of Ofatumumab
Measure Description MRTinf is the average amount of time that ofatumumab spends in the body. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.
Time Frame Day 1; Weeks 7 and 24  

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.
PK Parameter 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 
Participants Analyzed 
[Units: Participants]
 8 
Mean Residence Time (MRTinf) of Ofatumumab 
[Units: Hr]
Geometric Mean (95% Confidence Interval)
 
Day 1, n=8   18.417 
 (10.437 to 32.500) 
Week 7, n=8   478.105 
 (333.067 to 686.300) 
Week 24, n=7   463.945 
 (263.535 to 816.762) 

No statistical analysis provided for Mean Residence Time (MRTinf) of Ofatumumab



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


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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.


  More Information