A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia
Study Details
Study Description
Brief Summary
Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect.
This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks.
Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population.
10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect.
This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks.
Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population.
10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 2000 mg dose ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg |
Drug: ofatumumab 100 mg, 1000 mg / vial
ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With a Dose-limiting Toxicity (DLT) [Up to Week 8]
A DLT was defined as the following toxicological findings, according to the Common Terminology Criteria for Adverse Events (AE) v3.0: any treatment-related Grade (G) >=3 non-hematotoxic AE, occurrence of G3 infusion reaction (treatment-related AE) at the day of infusion in a participant who received pre-medication or appropriate management during infusion (glucocorticoid) (the severity of the AE must have remained as >= G3 until the next day); and any of following: >= G4 hematotoxic treatment-related AEs (neutropenia lasting 7 days or more, febrile neutropenia).
- 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 [Up to Week 48]
Par. were evaluated in accordance with the National Cancer Institute-sponsored Working Group. CR: no lymphadenopathy (Ly)/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils >=1.5*10^9/liter (L), platelets >100*10^9/L, hemoglobin >11.0 grams/deciliter, lymphocytes (LC) <4.0*10^9/L, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to chronic lymphocytic leukemia but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen, etc. nPR: nodules in BM.
Secondary Outcome Measures
- Progression-free Survival (PFS) as Assessed by a SERC [Up to Week 48]
PFS is defined as the time from the start of treatment to the first documented sign of progressive disease (PD) or death due to any cause (whichever occurs earlier).
- Duration of Response as Assessed by a SERC [Up to Week 48]
Duration of response is defined as the time from the first documented evidence of PR or better until the first documented sign of PD or death due to any reason in participants with PR or better.
- Overall Survival [Up to Week 48]
Overall survival is defined as the time from the first infusion of investigational drug to death due to any cause.
- Time to Response as Assessed by a SERC [Up to Week 48]
Time to response is defined as the time from the first infusion of investigational drug to the first response (PR or better).
- Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy as Assessed by a SERC [Up to Week 48]
Time to next CLL therapy is defined as the time from the first infusion of investigational drug to the first administration of the next CLL treatment. CLL therapy includes anti-cancer chemotherapy, anti-cancer radiotherapy, radio-immunotherapy, and antibody therapy.
- Mean Laboratory Data for Hemoglobin at the Indicated Weeks as Assessed by the Investigator [Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
Blood samples of the participants were collected for the assessment of hemoglobin.
- Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by the Investigator [Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
Blood samples of the participants were collected for the assessment of lymphocytes.
- Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator [Weeks 8, 16, 24, 36, and 48]
Bone marrow (BM) aspiration was performed, and the bone marrow smears were prepared for the assessment of lymphocytes in the BM.
- Mean Laboratory Data for Total Neutrophils (Total Absolute Neutrophil Count [ANC]) at the Indicated Weeks as Assessed by the Investigator [Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
Blood samples of the participants were collected for the assessment of total neutrophils.
- Mean Laboratory Data for Platelet Count at the Indicated Weeks as Assessed by the Investigator [Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
Blood samples of the participants were collected for the assessment of platelets.
- Percentage of Bone Marrow Infiltration at the Indicated Weeks as Assessed by a SERC [Weeks 8, 16, 24, 36, and 48]
SERC assessed bone marrow infiltration with the bone marrow smears of participants provided by trial sites.
- Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by a SERC [Weeks 8, 16, 24, 36, and 48]
SERC assessed lymphocytes based on the data provided by trial sites.
- Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by a SERC [Weeks 8, 16, 24, 36, and 48]
SERC assessed lymphocytes in the bone marrow (BM) based on the data with BM smears provided by trial sites.
- Mean Laboratory Data for Total Neutrophils (Total ANC) at the Indicated Weeks as Assessed by a SERC [Weeks 8, 16, 24, 36, and 48]
SERC assessed total neutrophils based on the data provided by trial sites.
- Number of Peripheral Blood Cluster of Differentiation (CD) CD19+ CD20+ Cells [Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48]
CD19+ CD20+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
- Number of Peripheral Blood CD20+ CD23+ Cells [Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48]
CD20+ CD23+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
- Number of Peripheral Blood CD19+ CD23+ Cells [Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48]
CD19+ CD23+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
- Number of Peripheral Blood CD19+ CD5+ Cells [Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48]
CD19+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
- Number of Peripheral Blood CD20+ CD5+ Cells [Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48]
CD20+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
- Number of Peripheral Blood CD23+ CD5+ Cells [Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48]
CD23+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.
- Ratio of Immunoglobulin (Ig) Kappa/Ig Lambda [Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48]
Peripheral blood Ig kappa and Ig lambda were measured using flow cytometry. Abnormality of a ratio of Ig kappa and Ig lambda indicates clonality of lymphocytes. A normal range of this parameter is between 1.0 and 3.2.
- Number of Participants With the Indicated Shift From Baseline (BL) in Night Sweats at the Indicated Weeks [Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
Night sweats are one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had night sweats at BL, and still had night sweats at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had night sweats at BL, but did not have night sweats at Week 1 are represented in the BL, yes; Week 1, no category.
- Number of Participants With the Indicated Shift From Baseline (BL) in Weight Loss at the Indicated Weeks [Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
Weight loss is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had weight loss at BL, and still had weight loss at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had weight loss at BL, but did not have weight loss at Week 1 are represented in the BL, yes; Week 1, no category.
- Number of Participants With the Indicated Shift From Baseline (BL) in Fever at the Indicated Weeks [Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
Fever is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had fever at BL, and still had fever at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had fever at BL, but did not have fever at Week 1 are represented in the BL, yes; Week 1, no category.
- Number of Participants With the Indicated Shift From Baseline (BL) in Extreme Fatigue at the Indicated Weeks [Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
Extreme fatigue is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had extreme fatigue at BL, and still had extreme fatigue at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had extreme fatigue at BL, but did not have extreme fatigue at Week 1 are represented in the BL, yes; Week 1, no category.
- Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Weeks 8, 24, and 48 [Baseline and Weeks 8, 24, and 48]
Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants.
- Number of Participants Who Tested Positive/Negative for Human Anti-human Antibodies (HAHA) at Screening and at Weeks 24 and 48 [Screening; Weeks 24 and 48]
HAHA are indicators of immunogenicity to ofatumumab.
- Number of Participants With a Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48]
ECOG PS is used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. The grades for the scale range from 0 (fully active) to 4 (completely disabled), with increasing severity.
- Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab [Day 1; Weeks 7 and 24]
Blood sampling on Day 1 and at Weeks 7 and 24 for pharmacokinetic (PK) evaluation was performed at the following time points: 0.5 hour (hr) before infusion; end of infusion; and 10 minutes (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.
- Minimum Plasma Concentration (Cmin) of Ofatumumab [Weeks 7 and 24]
Blood sampling 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), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.
- Time to Reach Cmax (Tmax) Following Ofatumumab Administration [Day 1; Weeks 7 and 24]
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.
- Half-life (t1/2) of Ofatumumab [Day 1; Weeks 7 and 24]
t1/2 of ofatumumab is the time required for the plasma concentration of ofatumumab to decrease by half. 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.
- Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for Ofatumumab [Day 1; Weeks 7 and 24]
AUC(0-t) was evaluated from the plasma concentration versus time curve from time zero to the last measurable time point (time t). 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.
- Area Under the Plasma Concentration-time Curve From Time Zero to 168 hr (AUC[0-168]) for Ofatumumab at Week 7 [Week 7]
Blood sampling at Week 7 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), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.
- Area Under the Plasma Concentration-time Curve From Time Zero to 672 hr (AUC[0-672]) for Ofatumumab at Week 24 [Week 24]
Blood sampling at Week 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), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab [Day 1; Weeks 7 and 24]
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.
- Clearance (CL) of Ofatumumab From Plasma [Day 1; Weeks 7 and 24]
CL of ofatumumab from plasma of participants was evaluated. 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.
- Volume of Distribution (Vz) During the Terminal Phase for Ofatumumab [Day 1; Weeks 7 and 24]
Vz for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body during the terminal phase to the plasma concentration during the terminal phase. 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.
- Volume of Distribution at Steady State (Vss) for Ofatumumab [Day 1; Weeks 7 and 24]
Vss for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body in equilibrium conditions to steady-state plasma concentrations. 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.
- Mean Residence Time (MRTinf) of Ofatumumab [Day 1; Weeks 7 and 24]
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.
Other Outcome Measures
- Serum Hemolytic Complement Titer at Weeks 36 and 48: CH50 [Weeks 36 and 48]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria at the time of screening:
-
Patients who gave consent to this study participation and signed into informed consent form.
-
Previously treated(Patients who received at least one prior CLL therapy and have either relapsed or have refractory disease, both requiring therapy.) CLL with at least 5 x 109 B lymphocytes/ L (5000/μL). The diagnosis of CLL requires CD5, CD19, CD20 and CD23 positivity, according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines [Hallek, 2008].
-
Laboratory test values meet the following criteria which indicate that patients have sufficient physiological functions;
Neutrophils:1≥ 500 /mm3 ALT ≤ 2.5 times upper local normal limit Creatinine ≤ 1.5 times upper local normal limit Total bilirubin≤ 1.5 times upper local normal limit
1:Patients should not receive any hematopoietic cytokine such as G-CSF preparations within 1 week before screening laboratory test for neutrophil counting.
- Patients who passed the following periods from the last anti-cancer treatments at the time of screening: At least 4 weeks after anti-cancer chemotherapy. At least 4 weeks after anti-cancer radiotherapy. At least 4 weeks after glucocorticoids treatment for CLL unless ≤ 10 mg of prednisolone /day.
At least 12 weeks after radio-immunotherapy and/or antibody therapy.
-
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.
-
Life expectancy more than 24 weeks after screening test.
-
Aged ≥ 20 (at the time of signing informed consent).
-
Patients possible to stay at the trial site for at least two days (the day of the first infusion and a subsequent day).
Exclusion Criteria:
A subject will not be eligible for inclusion in this study if any of the following criteria is met:
-
Active malignancy which needs therapy with anti-cancer drug, except for CLL.
-
Known Richter's transformation.
-
Previous autologous stem cell transplantation, within 24 weeks prior to screening.
-
Previous allogenic stem cell transplantation.
-
Known CNS involvement.
-
History of significant cerebrovascular disease.
-
Current cardiac disease requiring medical treatment (e.g. atrial flutter treated with acetylsalicylic acid and beta blocking agents).
-
Chronic or active infectious disease requiring systemic (intravenous or oral) treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.
-
Suspected/known immediate or delayed hypersensitivity to components of ofatumumab.
-
Patients previously treated with ofatumumab.
-
Positive serology test for any of HBsAg, anti-HBcAb or anti-HCVAb. If only anti-HBcAb results is positive, HBV-DNA test will be performed. If HBV-DNA results in negative, the patient is eligible.
-
HIV positivity.
-
Pregnant or lactating women.
-
Women of childbearing potential not willing to use adequate contraception during the study and one year after the last dose of ofatumumab, and male patients not willing to use adequate contraception during the study. Adequate contraception is defined as follows but not limited to; Abstinence. Oral Contraceptive (exclude oral progesterone alone). Intrauterine device (IUD) or intrauterine system (IUS). Male partner sterilization. Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (gel / film) etc.
-
Use of an investigational drug within 4 weeks prior to screening.
-
Current participation in any other clinical study.
-
Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
-
Patients who an investigator (or sub investigator) judges ineligible to this study.
Note; Child-bearing potential: a woman with functioning ovaries and uterine, or no documented sterility (i.e., a woman with functioning ovaries who have a current documented tubal ligation, women who have had a hysterectomy, women who are post-menopausal, or women who have had both ovaries surgically removed).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Aichi | Japan | 466-8650 | |
| 2 | GSK Investigational Site | Kanagawa | Japan | 259-1143 | |
| 3 | GSK Investigational Site | Nagasaki | Japan | 852-8501 | |
| 4 | GSK Investigational Site | Tokyo | Japan | 104-0045 | |
| 5 | GSK Investigational Site | Tokyo | Japan | 135-8550 | |
| 6 | GSK Investigational Site | Seoul | Korea, Republic of | 110-744 | |
| 7 | GSK Investigational Site | Seoul | Korea, Republic of | 138-736 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 112758
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 10 |
| COMPLETED | 7 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 10 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
66.3
(5.87)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
30%
|
| Male |
7
70%
|
| Race/Ethnicity, Customized (participants) [Number] | |
| Asian - East Asian Heritage |
1
10%
|
| Asian - Japanese Heritage |
9
90%
|
Outcome Measures
| Title | Number of Participants With a Dose-limiting Toxicity (DLT) |
|---|---|
| Description | A DLT was defined as the following toxicological findings, according to the Common Terminology Criteria for Adverse Events (AE) v3.0: any treatment-related Grade (G) >=3 non-hematotoxic AE, occurrence of G3 infusion reaction (treatment-related AE) at the day of infusion in a participant who received pre-medication or appropriate management during infusion (glucocorticoid) (the severity of the AE must have remained as >= G3 until the next day); and any of following: >= G4 hematotoxic treatment-related AEs (neutropenia lasting 7 days or more, febrile neutropenia). |
| Time Frame | Up to Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population: all participants who received at least one dose of investigational drug. The first 3 participants enrolled in the study were evaluated for DLT according to study design. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 3 |
| Number [participants] |
0
0%
|
| Title | 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 |
|---|---|
| Description | Par. were evaluated in accordance with the National Cancer Institute-sponsored Working Group. CR: no lymphadenopathy (Ly)/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils >=1.5*10^9/liter (L), platelets >100*10^9/L, hemoglobin >11.0 grams/deciliter, lymphocytes (LC) <4.0*10^9/L, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to chronic lymphocytic leukemia but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen, etc. nPR: nodules in BM. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| SERC |
70
700%
|
| Investigator |
70
700%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ofatumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | percentage of participants |
| Estimated Value | 70 | |
| Confidence Interval |
(2-Sided) 95% 34.8 to 93.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | SERC assessment | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ofatumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | percentage of participants |
| Estimated Value | 70 | |
| Confidence Interval |
(2-Sided) 95% 34.8 to 93.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Investigator assessment | |
| Title | Progression-free Survival (PFS) as Assessed by a SERC |
|---|---|
| Description | PFS is defined as the time from the start of treatment to the first documented sign of progressive disease (PD) or death due to any cause (whichever occurs earlier). |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population: only those participants who progressed or died during the study were evaluated. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 2 |
| Median (95% Confidence Interval) [Weeks] |
NA
|
| Title | Duration of Response as Assessed by a SERC |
|---|---|
| Description | Duration of response is defined as the time from the first documented evidence of PR or better until the first documented sign of PD or death due to any reason in participants with PR or better. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population: only those participants classified as responders for the assessment of objective response were evaluated. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 7 |
| Median (95% Confidence Interval) [Weeks] |
NA
|
| Title | Overall Survival |
|---|---|
| Description | Overall survival is defined as the time from the first infusion of investigational drug to death due to any cause. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Median (95% Confidence Interval) [Weeks] |
NA
|
| Title | Time to Response as Assessed by a SERC |
|---|---|
| Description | Time to response is defined as the time from the first infusion of investigational drug to the first response (PR or better). |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population: only those participants classified as responders for the assessment of objective response were evaluated. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 7 |
| Median (95% Confidence Interval) [Weeks] |
8.1
|
| Title | Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy as Assessed by a SERC |
|---|---|
| Description | Time to next CLL therapy is defined as the time from the first infusion of investigational drug to the first administration of the next CLL treatment. CLL therapy includes anti-cancer chemotherapy, anti-cancer radiotherapy, radio-immunotherapy, and antibody therapy. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population: only those participants who received CLL therapy were evaluated. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 2 |
| Median (95% Confidence Interval) [Weeks] |
NA
|
| Title | Mean Laboratory Data for Hemoglobin at the Indicated Weeks as Assessed by the Investigator |
|---|---|
| Description | Blood samples of the participants were collected for the assessment of hemoglobin. |
| Time Frame | Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
115.7
(15.44)
|
| Week 1, n=10 |
116.0
(15.46)
|
| Week 2, n=10 |
117.4
(16.37)
|
| Week 3, n=10 |
117.0
(18.68)
|
| Week 4, n=10 |
116.1
(18.53)
|
| Week 5, n=10 |
116.4
(17.83)
|
| Week 6, n=10 |
118.1
(16.25)
|
| Week 7, n=10 |
118.4
(20.06)
|
| Week 8, n=10 |
119.8
(20.35)
|
| Week 12, n=10 |
122.6
(20.55)
|
| Week 16, n=10 |
125.6
(21.08)
|
| Week 20, n=10 |
127.8
(21.81)
|
| Week 24, n=10 |
127.8
(22.31)
|
| Week 28, n=9 |
126.2
(21.49)
|
| Week 36, n=9 |
128.1
(20.91)
|
| Week 48, n=7 |
137.1
(11.01)
|
| Title | Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by the Investigator |
|---|---|
| Description | Blood samples of the participants were collected for the assessment of lymphocytes. |
| Time Frame | Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
42.6038
(41.66244)
|
| Week 1, n=10 |
29.6861
(33.19072)
|
| Week 2, n=10 |
8.2290
(6.76264)
|
| Week 3, n=10 |
6.9065
(6.81649)
|
| Week 4, n=10 |
4.0446
(2.70652)
|
| Week 5, n=10 |
2.9535
(1.47227)
|
| Week 6, n=10 |
2.8063
(1.43681)
|
| Week 7, n=10 |
2.4792
(1.20853)
|
| Week 8, n=10 |
2.1515
(0.94237)
|
| Week 12, n=10 |
1.8058
(0.95653)
|
| Week 16, n=10 |
1.9575
(1.09880)
|
| Week 20, n=10 |
1.8388
(1.22494)
|
| Week 24, n=10 |
1.8500
(1.33979)
|
| Week 28, n=9 |
1.6405
(1.05653)
|
| Week 36, n=9 |
3.5754
(5.38456)
|
| Week 48, n=7 |
1.5099
(0.72285)
|
| Title | Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| 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)
|
| Title | Mean Laboratory Data for Total Neutrophils (Total Absolute Neutrophil Count [ANC]) at the Indicated Weeks as Assessed by the Investigator |
|---|---|
| Description | Blood samples of the participants were collected for the assessment of total neutrophils. |
| Time Frame | Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
4.3103
(1.91880)
|
| Week 1, n=10 |
3.9316
(2.37732)
|
| Week 2, n=10 |
3.2158
(1.62185)
|
| Week 3, n=10 |
2.7873
(1.16531)
|
| Week 4, n=10 |
2.4570
(1.22611)
|
| Week 5, n=10 |
2.3908
(0.99250)
|
| Week 6, n=10 |
2.1747
(1.00743)
|
| Week 7, n=10 |
2.1612
(1.22393)
|
| Week 8, n=10 |
2.2136
(1.22993)
|
| Week 12, n=10 |
1.9814
(0.90783)
|
| Week 16, n=10 |
1.9915
(1.00746)
|
| Week 20, n=10 |
2.2165
(1.29881)
|
| Week 24, n=10 |
2.3093
(1.18840)
|
| Week 28, n=9 |
2.2069
(1.57995)
|
| Week 36, n=9 |
2.3482
(1.04228)
|
| Week 48, n=7 |
3.0431
(1.67580)
|
| Title | Mean Laboratory Data for Platelet Count at the Indicated Weeks as Assessed by the Investigator |
|---|---|
| Description | Blood samples of the participants were collected for the assessment of platelets. |
| Time Frame | Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
106.5
(31.69)
|
| Week 1, n=10 |
104.0
(45.45)
|
| Week 2, n=10 |
100.1
(37.21)
|
| Week 3, n=10 |
118.3
(40.90)
|
| Week 4, n=10 |
114.9
(46.26)
|
| Week 5, n=10 |
111.5
(47.11)
|
| Week 6, n=10 |
115.7
(49.86)
|
| Week 7, n=10 |
121.4
(54.65)
|
| Week 8, n=10 |
127.7
(64.44)
|
| Week 12, n=10 |
120.1
(46.29)
|
| Week 16, n=10 |
124.3
(46.00)
|
| Week 20, n=10 |
134.0
(41.66)
|
| Week 24, n=10 |
136.6
(44.14)
|
| Week 28, n=9 |
128.9
(41.64)
|
| Week 36, n=9 |
143.0
(43.19)
|
| Week 48, n=7 |
130.7
(53.70)
|
| Title | Percentage of Bone Marrow Infiltration at the Indicated Weeks as Assessed by a SERC |
|---|---|
| Description | SERC assessed bone marrow infiltration with the bone marrow smears of participants provided by trial sites. |
| Time Frame | Weeks 8, 16, 24, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| 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 |
29.13
(17.379)
|
| Week 48, n=5 |
23.26
(9.651)
|
| Title | Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by a SERC |
|---|---|
| Description | SERC assessed lymphocytes based on the data provided by trial sites. |
| Time Frame | Weeks 8, 16, 24, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Week 8, n=8 |
2.0120
(1.03095)
|
| Week 16, n=6 |
1.7975
(1.05163)
|
| Week 24, n=7 |
1.8784
(1.56286)
|
| Week 36, n=6 |
2.1213
(2.65560)
|
| Week 48, n=5 |
1.6284
(0.70741)
|
| Title | Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by a SERC |
|---|---|
| Description | SERC assessed lymphocytes in the bone marrow (BM) based on the data with BM smears provided by trial sites. |
| Time Frame | Weeks 8, 16, 24, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| 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 |
29.13
(17.379)
|
| Week 48, n=5 |
23.26
(9.651)
|
| Title | Mean Laboratory Data for Total Neutrophils (Total ANC) at the Indicated Weeks as Assessed by a SERC |
|---|---|
| Description | SERC assessed total neutrophils based on the data provided by trial sites. |
| Time Frame | Weeks 8, 16, 24, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Week 8, n=8 |
2.3159
(1.35507)
|
| Week 16, n=6 |
2.5803
(1.04075)
|
| Week 24, n=7 |
2.8706
(1.39803)
|
| Week 36, n=6 |
2.1957
(0.89898)
|
| Week 48, n=5 |
2.6242
(1.05912)
|
| Title | Number of Peripheral Blood Cluster of Differentiation (CD) CD19+ CD20+ Cells |
|---|---|
| Description | CD19+ CD20+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. |
| Time Frame | Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
33.1140
(39.40966)
|
| Week 1, n=9 |
19.6438
(35.81756)
|
| Week 2, n=10 |
0.0060
(0.01151)
|
| Week 4, n=10 |
0.0565
(0.16699)
|
| Week 6, n=10 |
0.0022
(0.00258)
|
| Week 8, n=9 |
0.0006
(0.00136)
|
| Week 12, n=10 |
0.0006
(0.00116)
|
| Week 16, n=10 |
0.0003
(0.00058)
|
| Week 20, n=10 |
0.0005
(0.00087)
|
| Week 24, n=10 |
0.0002
(0.00037)
|
| Week 28, n=9 |
0.0003
(0.00093)
|
| Week 36, n=8 |
0.2525
(0.71266)
|
| Week 48, n=7 |
0.0914
(0.10259)
|
| Title | Number of Peripheral Blood CD20+ CD23+ Cells |
|---|---|
| Description | CD20+ CD23+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. |
| Time Frame | Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
19.9791
(27.06441)
|
| Week 1, n=9 |
8.9466
(21.59662)
|
| Week 2, n=10 |
0.0319
(0.04010)
|
| Week 4, n=10 |
0.0685
(0.14483)
|
| Week 6, n=10 |
0.0099
(0.01869)
|
| Week 8, n=9 |
0.0047
(0.01131)
|
| Week 12, n=10 |
0.0080
(0.02270)
|
| Week 16, n=10 |
0.0111
(0.03162)
|
| Week 20, n=10 |
0.0048
(0.01277)
|
| Week 24, n=10 |
0.0057
(0.01553)
|
| Week 28, n=9 |
0.0002
(0.00040)
|
| Week 36, n=8 |
0.2147
(0.60466)
|
| Week 48, n=7 |
0.0773
(0.09355)
|
| Title | Number of Peripheral Blood CD19+ CD23+ Cells |
|---|---|
| Description | CD19+ CD23+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. |
| Time Frame | Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
23.8046
(28.66936)
|
| Week 1, n=9 |
17.4769
(22.30923)
|
| Week 2, n=10 |
4.6972
(6.14672)
|
| Week 4, n=10 |
1.8230
(2.49206)
|
| Week 6, n=10 |
0.4858
(0.55687)
|
| Week 8, n=9 |
0.2252
(0.25765)
|
| Week 12, n=10 |
0.2122
(0.26787)
|
| Week 16, n=10 |
0.1961
(0.34108)
|
| Week 20, n=10 |
0.1464
(0.33132)
|
| Week 24, n=10 |
0.1330
(0.23961)
|
| Week 28, n=9 |
0.1123
(0.26130)
|
| Week 36, n=8 |
0.2687
(0.71524)
|
| Week 48, n=7 |
0.0886
(0.11398)
|
| Title | Number of Peripheral Blood CD19+ CD5+ Cells |
|---|---|
| Description | CD19+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. |
| Time Frame | Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
36.0022
(36.64910)
|
| Week 1, n=9 |
27.9129
(32.61649)
|
| Week 2, n=10 |
5.4212
(6.55286)
|
| Week 4, n=10 |
2.2158
(2.62609)
|
| Week 6, n=10 |
0.5799
(0.63484)
|
| Week 8, n=9 |
0.2338
(0.27058)
|
| Week 12, n=10 |
0.2420
(0.32493)
|
| Week 16, n=10 |
0.2425
(0.38048)
|
| Week 20, n=10 |
0.1943
(0.38386)
|
| Week 24, n=10 |
0.1719
(0.29401)
|
| Week 28, n=9 |
0.1449
(0.25617)
|
| Week 36, n=8 |
0.2858
(0.73543)
|
| Week 48, n=7 |
0.1200
(0.14511)
|
| Title | Number of Peripheral Blood CD20+ CD5+ Cells |
|---|---|
| Description | CD20+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. |
| Time Frame | Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
32.9606
(39.50102)
|
| Week 1, n=9 |
19.3999
(35.56146)
|
| Week 2, n=10 |
0.0134
(0.01696)
|
| Week 4, n=10 |
0.0493
(0.13576)
|
| Week 6, n=10 |
0.0024
(0.00185)
|
| Week 8, n=9 |
0.0029
(0.00136)
|
| Week 12, n=10 |
0.0020
(0.00160)
|
| Week 16, n=10 |
0.0062
(0.00907)
|
| Week 20, n=10 |
0.0026
(0.00147)
|
| Week 24, n=10 |
0.0036
(0.00258)
|
| Week 28, n=9 |
0.0022
(0.00214)
|
| Week 36, n=8 |
0.2597
(0.72781)
|
| Week 48, n=7 |
0.0968
(0.11682)
|
| Title | Number of Peripheral Blood CD23+ CD5+ Cells |
|---|---|
| Description | CD23+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. |
| Time Frame | Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
22.7190
(25.17338)
|
| Week 1, n=9 |
17.2018
(21.23454)
|
| Week 2, n=10 |
4.5264
(6.03353)
|
| Week 4, n=10 |
1.8255
(2.49671)
|
| Week 6, n=10 |
0.4714
(0.50306)
|
| Week 8, n=9 |
0.2095
(0.23907)
|
| Week 12, n=10 |
0.2114
(0.27306)
|
| Week 16, n=10 |
0.1866
(0.34514)
|
| Week 20, n=10 |
0.1478
(0.32088)
|
| Week 24, n=10 |
0.1327
(0.23698)
|
| Week 28, n=9 |
0.1035
(0.23789)
|
| Week 36, n=8 |
0.2570
(0.68983)
|
| Week 48, n=7 |
0.1062
(0.13388)
|
| Title | Ratio of Immunoglobulin (Ig) Kappa/Ig Lambda |
|---|---|
| Description | Peripheral blood Ig kappa and Ig lambda were measured using flow cytometry. Abnormality of a ratio of Ig kappa and Ig lambda indicates clonality of lymphocytes. A normal range of this parameter is between 1.0 and 3.2. |
| Time Frame | Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Day 1, n=10 |
34.710
(38.2375)
|
| Week 1, n=9 |
36.604
(36.9383)
|
| Week 2, n=10 |
15.928
(26.5203)
|
| Week 4, n=10 |
9.451
(25.1555)
|
| Week 6, n=10 |
7.263
(20.3014)
|
| Week 8, n=9 |
6.427
(16.7389)
|
| Week 12, n=10 |
3.799
(8.8774)
|
| Week 16, n=10 |
2.150
(3.8972)
|
| Week 20, n=10 |
2.017
(3.8733)
|
| Week 24, n=10 |
1.608
(2.6223)
|
| Week 28, n=9 |
1.647
(2.3965)
|
| Week 36, n=8 |
1.693
(1.8636)
|
| Week 48, n=7 |
3.368
(5.2575)
|
| Title | Number of Participants With the Indicated Shift From Baseline (BL) in Night Sweats at the Indicated Weeks |
|---|---|
| Description | Night sweats are one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had night sweats at BL, and still had night sweats at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had night sweats at BL, but did not have night sweats at Week 1 are represented in the BL, yes; Week 1, no category. |
| Time Frame | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| BL, yes; Week 1, yes; n=10 |
1
10%
|
| BL, yes; Week 1, no; n=10 |
0
0%
|
| BL, no; Week 1, yes; n=10 |
0
0%
|
| BL, no; Week 1, no; n=10 |
9
90%
|
| BL, yes; Week 2, yes; n=10 |
1
10%
|
| BL, yes; Week 2, no; n=10 |
0
0%
|
| BL, no; Week 2, yes; n=10 |
0
0%
|
| BL, no; Week 2, no; n=10 |
9
90%
|
| BL, yes; Week 3, yes; n=10 |
1
10%
|
| BL, yes; Week 3, no; n=10 |
0
0%
|
| BL, no; Week 3, yes; n=10 |
0
0%
|
| BL, no; Week 3, no; n=10 |
9
90%
|
| BL, yes; Week 4, yes; n=10 |
1
10%
|
| BL, yes; Week 4, no; n=10 |
0
0%
|
| BL, no; Week 4, yes; n=10 |
0
0%
|
| BL, no; Week 4, no; n=10 |
9
90%
|
| BL, yes; Week 5, yes; n=10 |
0
0%
|
| BL, yes; Week 5, no; n=10 |
0
0%
|
| BL, no; Week 5, yes; n=10 |
1
10%
|
| BL, no; Week 5, no; n=10 |
9
90%
|
| BL, yes; Week 6, yes; n=10 |
0
0%
|
| BL, yes; Week 6, no; n=10 |
0
0%
|
| BL, no; Week 6, yes; n=10 |
1
10%
|
| BL, no; Week 6, no; n=10 |
9
90%
|
| BL, yes; Week 7, yes; n=10 |
0
0%
|
| BL, yes; Week 7, no; n=10 |
0
0%
|
| BL, no; Week 7, yes; n=10 |
1
10%
|
| BL, no; Week 7, no; n=10 |
9
90%
|
| BL, yes; Week 8, yes; n=10 |
0
0%
|
| BL, yes; Week 8, no; n=10 |
0
0%
|
| BL, no; Week 8, yes; n=10 |
1
10%
|
| BL, no; Week 8, no; n=10 |
9
90%
|
| BL, yes; Week 12, yes; n=10 |
0
0%
|
| BL, yes; Week 12, no; n=10 |
0
0%
|
| BL, no; Week 12, yes; n=10 |
1
10%
|
| BL, no; Week 12, no; n=10 |
9
90%
|
| BL, yes; Week 16, yes; n=10 |
0
0%
|
| BL, yes; Week 16, no; n=10 |
0
0%
|
| BL, no; Week 16, yes; n=10 |
1
10%
|
| BL, no; Week 16, no; n=10 |
9
90%
|
| BL, yes; Week 20, yes; n=10 |
0
0%
|
| BL, yes; Week 20, no; n=10 |
0
0%
|
| BL, no; Week 20, yes; n=10 |
1
10%
|
| BL, no; Week 20, no; n=10 |
9
90%
|
| BL, yes; Week 24, yes; n=10 |
0
0%
|
| BL, yes; Week 24, no; n=10 |
0
0%
|
| BL, no; Week 24, yes; n=10 |
1
10%
|
| BL, no; Week 24, no; n=10 |
9
90%
|
| BL, yes; Week 28, yes; n=9 |
0
0%
|
| BL, yes; Week 28, no; n=9 |
0
0%
|
| BL, no; Week 28, yes; n=9 |
1
10%
|
| BL, no; Week 28, no; n=9 |
8
80%
|
| BL, yes; Week 36, yes; n=9 |
0
0%
|
| BL, yes; Week 36, no; n=9 |
0
0%
|
| BL, no; Week 36, yes; n=9 |
1
10%
|
| BL, no; Week 36, no; n=9 |
8
80%
|
| BL, yes; Week 48, yes; n=7 |
0
0%
|
| BL, yes; Week 48, no; n=7 |
0
0%
|
| BL, no; Week 48, yes; n=7 |
0
0%
|
| BL, no; Week 48, no; n=7 |
7
70%
|
| Title | Number of Participants With the Indicated Shift From Baseline (BL) in Weight Loss at the Indicated Weeks |
|---|---|
| Description | Weight loss is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had weight loss at BL, and still had weight loss at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had weight loss at BL, but did not have weight loss at Week 1 are represented in the BL, yes; Week 1, no category. |
| Time Frame | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| BL, yes; Week 1, yes; n=10 |
0
0%
|
| BL, yes; Week 1, no; n=10 |
0
0%
|
| BL, no; Week 1, yes; n=10 |
0
0%
|
| BL, no; Week 1, no; n=10 |
10
100%
|
| BL, yes; Week 2, yes; n=10 |
0
0%
|
| BL, yes; Week 2, no; n=10 |
0
0%
|
| BL, no; Week 2, yes; n=10 |
0
0%
|
| BL, no; Week 2, no; n=10 |
10
100%
|
| BL, yes; Week 3, yes; n=10 |
0
0%
|
| BL, yes; Week 3, no; n=10 |
0
0%
|
| BL, no; Week 3, yes; n=10 |
0
0%
|
| BL, no; Week 3, no; n=10 |
10
100%
|
| BL, yes; Week 4, yes; n=10 |
0
0%
|
| BL, yes; Week 4, no; n=10 |
0
0%
|
| BL, no; Week 4, yes; n=10 |
0
0%
|
| BL, no; Week 4, no; n=10 |
10
100%
|
| BL, yes; Week 5, yes; n=10 |
0
0%
|
| BL, yes; Week 5, no; n=10 |
0
0%
|
| BL, no; Week 5, yes; n=10 |
0
0%
|
| BL, no; Week 5, no; n=10 |
10
100%
|
| BL, yes; Week 6, yes; n=10 |
0
0%
|
| BL, yes; Week 6, no; n=10 |
0
0%
|
| BL, no; Week 6, yes; n=10 |
0
0%
|
| BL, no; Week 6, no; n=10 |
10
100%
|
| BL, yes; Week 7, yes; n=10 |
0
0%
|
| BL, yes; Week 7, no; n=10 |
0
0%
|
| BL, no; Week 7, yes; n=10 |
0
0%
|
| BL, no; Week 7, no; n=10 |
10
100%
|
| BL, yes; Week 8, yes; n=10 |
0
0%
|
| BL, yes; Week 8, no; n=10 |
0
0%
|
| BL, no; Week 8, yes; n=10 |
0
0%
|
| BL, no; Week 8, no; n=10 |
10
100%
|
| BL, yes; Week 12, yes; n=10 |
0
0%
|
| BL, yes; Week 12, no; n=10 |
0
0%
|
| BL, no; Week 12, yes; n=10 |
0
0%
|
| BL, no; Week 12, no; n=10 |
10
100%
|
| BL, yes; Week 16, yes; n=10 |
0
0%
|
| BL, yes; Week 16, no; n=10 |
0
0%
|
| BL, no; Week 16, yes; n=10 |
0
0%
|
| BL, no; Week 16, no; n=10 |
10
100%
|
| BL, yes; Week 20, yes; n=10 |
0
0%
|
| BL, yes; Week 20, no; n=10 |
0
0%
|
| BL, no; Week 20, yes; n=10 |
0
0%
|
| BL, no; Week 20, no; n=10 |
10
100%
|
| BL, yes; Week 24, yes; n=10 |
0
0%
|
| BL, yes; Week 24, no; n=10 |
0
0%
|
| BL, no; Week 24, yes; n=10 |
0
0%
|
| BL, no; Week 24, no; n=10 |
10
100%
|
| BL, yes; Week 28, yes; n=9 |
0
0%
|
| BL, yes; Week 28, no; n=9 |
0
0%
|
| BL, no; Week 28, yes; n=9 |
0
0%
|
| BL, no; Week 28, no; n=9 |
9
90%
|
| BL, yes; Week 36, yes; n=9 |
0
0%
|
| BL, yes; Week 36, no; n=9 |
0
0%
|
| BL, no; Week 36, yes; n=9 |
0
0%
|
| BL, no; Week 36, no; n=9 |
9
90%
|
| BL, yes; Week 48, yes; n=7 |
0
0%
|
| BL, yes; Week 48, no; n=7 |
0
0%
|
| BL, no; Week 48, yes; n=7 |
0
0%
|
| BL, no; Week 48, no; n=7 |
7
70%
|
| Title | Number of Participants With the Indicated Shift From Baseline (BL) in Fever at the Indicated Weeks |
|---|---|
| Description | Fever is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had fever at BL, and still had fever at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had fever at BL, but did not have fever at Week 1 are represented in the BL, yes; Week 1, no category. |
| Time Frame | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| BL, yes; Week 1, yes; n=10 |
0
0%
|
| BL, yes; Week 1, no; n=10 |
0
0%
|
| BL, no; Week 1, yes; n=10 |
0
0%
|
| BL, no; Week 1, no; n=10 |
10
100%
|
| BL, yes; Week 2, yes; n=10 |
0
0%
|
| BL, yes; Week 2, no; n=10 |
0
0%
|
| BL, no; Week 2, yes; n=10 |
0
0%
|
| BL, no; Week 2, no; n=10 |
10
100%
|
| BL, yes; Week 3, yes; n=10 |
0
0%
|
| BL, yes; Week 3, no; n=10 |
0
0%
|
| BL, no; Week 3, yes; n=10 |
0
0%
|
| BL, no; Week 3, no; n=10 |
10
100%
|
| BL, yes; Week 4, yes; n=10 |
0
0%
|
| BL, yes; Week 4, no; n=10 |
0
0%
|
| BL, no; Week 4, yes; n=10 |
0
0%
|
| BL, no; Week 4, no; n=10 |
10
100%
|
| BL, yes; Week 5, yes; n=10 |
0
0%
|
| BL, yes; Week 5, no; n=10 |
0
0%
|
| BL, no; Week 5, yes; n=10 |
0
0%
|
| BL, no; Week 5, no; n=10 |
10
100%
|
| BL, yes; Week 6, yes; n=10 |
0
0%
|
| BL, yes; Week 6, no; n=10 |
0
0%
|
| BL, no; Week 6, yes; n=10 |
0
0%
|
| BL, no; Week 6, no; n=10 |
10
100%
|
| BL, yes; Week 7, yes; n=10 |
0
0%
|
| BL, yes; Week 7, no; n=10 |
0
0%
|
| BL, no; Week 7, yes; n=10 |
0
0%
|
| BL, no; Week 7, no; n=10 |
10
100%
|
| BL, yes; Week 8, yes; n=10 |
0
0%
|
| BL, yes; Week 8, no; n=10 |
0
0%
|
| BL, no; Week 8, yes; n=10 |
0
0%
|
| BL, no; Week 8, no; n=10 |
10
100%
|
| BL, yes; Week 12, yes; n=10 |
0
0%
|
| BL, yes; Week 12, no; n=10 |
0
0%
|
| BL, no; Week 12, yes; n=10 |
0
0%
|
| BL, no; Week 12, no; n=10 |
10
100%
|
| BL, yes; Week 16, yes; n=10 |
0
0%
|
| BL, yes; Week 16, no; n=10 |
0
0%
|
| BL, no; Week 16, yes; n=10 |
0
0%
|
| BL, no; Week 16, no; n=10 |
10
100%
|
| BL, yes; Week 20, yes; n=10 |
0
0%
|
| BL, yes; Week 20, no; n=10 |
0
0%
|
| BL, no; Week 20, yes; n=10 |
0
0%
|
| BL, no; Week 20, no; n=10 |
10
100%
|
| BL, yes; Week 24, yes; n=10 |
0
0%
|
| BL, yes; Week 24, no; n=10 |
0
0%
|
| BL, no; Week 24, yes; n=10 |
0
0%
|
| BL, no; Week 24, no; n=10 |
10
100%
|
| BL, yes; Week 28, yes; n=9 |
0
0%
|
| BL, yes; Week 28, no; n=9 |
0
0%
|
| BL, no; Week 28, yes; n=9 |
0
0%
|
| BL, no; Week 28, no; n=9 |
9
90%
|
| BL, yes; Week 36, yes; n=9 |
0
0%
|
| BL, yes; Week 36, no; n=9 |
0
0%
|
| BL, no; Week 36, yes; n=9 |
0
0%
|
| BL, no; Week 36, no; n=9 |
9
90%
|
| BL, yes; Week 48, yes; n=7 |
0
0%
|
| BL, yes; Week 48, no; n=7 |
0
0%
|
| BL, no; Week 48, yes; n=7 |
0
0%
|
| BL, no; Week 48, no; n=7 |
7
70%
|
| Title | Number of Participants With the Indicated Shift From Baseline (BL) in Extreme Fatigue at the Indicated Weeks |
|---|---|
| Description | Extreme fatigue is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had extreme fatigue at BL, and still had extreme fatigue at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had extreme fatigue at BL, but did not have extreme fatigue at Week 1 are represented in the BL, yes; Week 1, no category. |
| Time Frame | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| BL, yes; Week 1, yes; n=10 |
0
0%
|
| BL, yes; Week 1, no; n=10 |
0
0%
|
| BL, no; Week 1, yes; n=10 |
0
0%
|
| BL, no; Week 1, no; n=10 |
10
100%
|
| BL, yes; Week 2, yes; n=10 |
0
0%
|
| BL, yes; Week 2, no; n=10 |
0
0%
|
| BL, no; Week 2, yes; n=10 |
0
0%
|
| BL, no; Week 2, no; n=10 |
10
100%
|
| BL, yes; Week 3, yes; n=10 |
0
0%
|
| BL, yes; Week 3, no; n=10 |
0
0%
|
| BL, no; Week 3, yes; n=10 |
0
0%
|
| BL, no; Week 3, no; n=10 |
10
100%
|
| BL, yes; Week 4, yes; n=10 |
0
0%
|
| BL, yes; Week 4, no; n=10 |
0
0%
|
| BL, no; Week 4, yes; n=10 |
0
0%
|
| BL, no; Week 4, no; n=10 |
10
100%
|
| BL, yes; Week 5, yes; n=10 |
0
0%
|
| BL, yes; Week 5, no; n=10 |
0
0%
|
| BL, no; Week 5, yes; n=10 |
0
0%
|
| BL, no; Week 5, no; n=10 |
10
100%
|
| BL, yes; Week 6, yes; n=10 |
0
0%
|
| BL, yes; Week 6, no; n=10 |
0
0%
|
| BL, no; Week 6, yes; n=10 |
0
0%
|
| BL, no; Week 6, no; n=10 |
10
100%
|
| BL, yes; Week 7, yes; n=10 |
0
0%
|
| BL, yes; Week 7, no; n=10 |
0
0%
|
| BL, no; Week 7, yes; n=10 |
0
0%
|
| BL, no; Week 7, no; n=10 |
10
100%
|
| BL, yes; Week 8, yes; n=10 |
0
0%
|
| BL, yes; Week 8, no; n=10 |
0
0%
|
| BL, no; Week 8, yes; n=10 |
0
0%
|
| BL, no; Week 8, no; n=10 |
10
100%
|
| BL, yes; Week 12, yes; n=10 |
0
0%
|
| BL, yes; Week 12, no; n=10 |
0
0%
|
| BL, no; Week 12, yes; n=10 |
0
0%
|
| BL, no; Week 12, no; n=10 |
10
100%
|
| BL, yes; Week 16, yes; n=10 |
0
0%
|
| BL, yes; Week 16, no; n=10 |
0
0%
|
| BL, no; Week 16, yes; n=10 |
0
0%
|
| BL, no; Week 16, no; n=10 |
10
100%
|
| BL, yes; Week 20, yes; n=10 |
0
0%
|
| BL, yes; Week 20, no; n=10 |
0
0%
|
| BL, no; Week 20, yes; n=10 |
0
0%
|
| BL, no; Week 20, no; n=10 |
10
100%
|
| BL, yes; Week 24, yes; n=10 |
0
0%
|
| BL, yes; Week 24, no; n=10 |
0
0%
|
| BL, no; Week 24, yes; n=10 |
0
0%
|
| BL, no; Week 24, no; n=10 |
10
100%
|
| BL, yes; Week 28, yes; n=9 |
0
0%
|
| BL, yes; Week 28, no; n=9 |
0
0%
|
| BL, no; Week 28, yes; n=9 |
0
0%
|
| BL, no; Week 28, no; n=9 |
9
90%
|
| BL, yes; Week 36, yes; n=9 |
0
0%
|
| BL, yes; Week 36, no; n=9 |
0
0%
|
| BL, no; Week 36, yes; n=9 |
0
0%
|
| BL, no; Week 36, no; n=9 |
9
90%
|
| BL, yes; Week 48, yes; n=7 |
0
0%
|
| BL, yes; Week 48, no; n=7 |
0
0%
|
| BL, no; Week 48, yes; n=7 |
0
0%
|
| BL, no; Week 48, no; n=7 |
7
70%
|
| Title | Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Weeks 8, 24, and 48 |
|---|---|
| Description | Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. |
| Time Frame | Baseline and Weeks 8, 24, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| IgA, Week 8, n=9 |
0.014
(0.1337)
|
| IgA, Week 24, n=9 |
-0.023
(0.0865)
|
| IgA, Week 48, n=7 |
0.086
(0.2889)
|
| IgG, Week 8, n=9 |
0.647
(0.9004)
|
| IgG, Week 24, n=10 |
-0.150
(0.8641)
|
| IgG, Week 48, n=7 |
-0.587
(0.9680)
|
| IgM, Week 8, n=7 |
-0.063
(0.1482)
|
| IgM, Week 24, n=8 |
-0.058
(0.1831)
|
| IgM, Week 48, n=5 |
-0.108
(0.1809)
|
| Title | Number of Participants Who Tested Positive/Negative for Human Anti-human Antibodies (HAHA) at Screening and at Weeks 24 and 48 |
|---|---|
| Description | HAHA are indicators of immunogenicity to ofatumumab. |
| Time Frame | Screening; Weeks 24 and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Positive at Screening, n=10 |
0
0%
|
| Negative at Screening, n=10 |
10
100%
|
| Positive at Week 24, n=10 |
0
0%
|
| Negative at Week 24, n=10 |
10
100%
|
| Positive at Week 48, n=7 |
0
0%
|
| Negative at Week 48, n=7 |
7
70%
|
| Title | Number of Participants With a Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) |
|---|---|
| Description | ECOG PS is used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. The grades for the scale range from 0 (fully active) to 4 (completely disabled), with increasing severity. |
| Time Frame | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Week 1, improved; n=10 |
0
0%
|
| Week 1, deteriorated; n=10 |
0
0%
|
| Week 2, improved; n=10 |
0
0%
|
| Week 2, deteriorated; n=10 |
0
0%
|
| Week 3, improved; n=10 |
0
0%
|
| Week 3, deteriorated; n=10 |
0
0%
|
| Week 4, improved; n=10 |
0
0%
|
| Week 4, deteriorated; n=10 |
0
0%
|
| Week 5, improved; n=10 |
0
0%
|
| Week 5, deteriorated; n=10 |
0
0%
|
| Week 6, improved; n=10 |
0
0%
|
| Week 6, deteriorated; n=10 |
0
0%
|
| Week 7, improved; n=10 |
0
0%
|
| Week 7, deteriorated; n=10 |
0
0%
|
| Week 8, improved; n=10 |
0
0%
|
| Week 8, deteriorated; n=10 |
0
0%
|
| Week 12, improved; n=10 |
0
0%
|
| Week 12, deteriorated; n=10 |
0
0%
|
| Week 16, improved; n=10 |
0
0%
|
| Week 16, deteriorated; n=10 |
0
0%
|
| Week 20, improved; n=10 |
0
0%
|
| Week 20, deteriorated; n=10 |
0
0%
|
| Week 24, improved; n=10 |
0
0%
|
| Week 24, deteriorated; n=10 |
0
0%
|
| Week 28, improved; n=9 |
0
0%
|
| Week 28, deteriorated; n=9 |
0
0%
|
| Week 36, improved; n=9 |
0
0%
|
| Week 36, deteriorated; n=9 |
0
0%
|
| Week 48, improved; n=7 |
0
0%
|
| Week 48, deteriorated; n=7 |
0
0%
|
| Title | Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab |
|---|---|
| Description | Blood sampling on Day 1 and at Weeks 7 and 24 for pharmacokinetic (PK) evaluation was performed at the following time points: 0.5 hour (hr) before infusion; end of infusion; and 10 minutes (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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population: all participants who received at least one dose of investigational drug, and in whom PK data were available and allowed parameter estimations. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
69.33
|
| Week 7, n=8 |
1670.36
|
| Week 24, n=7 |
864.93
|
| Title | Minimum Plasma Concentration (Cmin) of Ofatumumab |
|---|---|
| Description | Blood sampling 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), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab. |
| Time Frame | Weeks 7 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Week 7 |
832.17
|
| Week 24 |
122.08
|
| Title | Time to Reach Cmax (Tmax) Following Ofatumumab Administration |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
7.208
|
| Week 7, n=8 |
5.225
|
| Week 24, n=7 |
5.250
|
| Title | Half-life (t1/2) of Ofatumumab |
|---|---|
| Description | t1/2 of ofatumumab is the time required for the plasma concentration of ofatumumab to decrease by half. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
9.585
|
| Week 7, n=8 |
331.275
|
| Week 24, n=7 |
300.354
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for Ofatumumab |
|---|---|
| Description | AUC(0-t) was evaluated from the plasma concentration versus time curve from time zero to the last measurable time point (time t). 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
1345.1
|
| Week 7, n=8 |
587711.3
|
| Week 24, n=7 |
283751.4
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to 168 hr (AUC[0-168]) for Ofatumumab at Week 7 |
|---|---|
| Description | Blood sampling at Week 7 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), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab. |
| Time Frame | Week 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Geometric Mean (95% Confidence Interval) [hr*mcg/mL] |
200181.8
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to 672 hr (AUC[0-672]) for Ofatumumab at Week 24 |
|---|---|
| Description | Blood sampling at Week 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), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 7 |
| Geometric Mean (95% Confidence Interval) [hr*mcg/mL] |
216678.1
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
1506.3
|
| Week 7, n=8 |
716924.6
|
| Week 24, n=7 |
302326.7
|
| Title | Clearance (CL) of Ofatumumab From Plasma |
|---|---|
| Description | CL of ofatumumab from plasma of participants was evaluated. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
199.157
|
| Week 7, n=8 |
9.991
|
| Week 24, n=7 |
9.230
|
| Title | Volume of Distribution (Vz) During the Terminal Phase for Ofatumumab |
|---|---|
| Description | Vz for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body during the terminal phase to the plasma concentration during the terminal phase. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
2754.1
|
| Week 7, n=8 |
4774.9
|
| Week 24, n=7 |
3999.7
|
| Title | Volume of Distribution at Steady State (Vss) for Ofatumumab |
|---|---|
| Description | Vss for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body in equilibrium conditions to steady-state plasma concentrations. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
3667.9
|
| Week 7, n=8 |
1333.8
|
| Week 24, n=7 |
3069.2
|
| Title | Mean Residence Time (MRTinf) of Ofatumumab |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Parameter Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Day 1, n=8 |
18.417
|
| Week 7, n=8 |
478.105
|
| Week 24, n=7 |
463.945
|
| Title | Serum Hemolytic Complement Titer at Weeks 36 and 48: CH50 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed. |
| Arm/Group Title | Ofatumumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 |
| Week 36, n=8 |
45.14
(13.643)
|
| Week 48, n=7 |
53.70
(11.818)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Ofatumumab | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Ofatumumab | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Ofatumumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/10 (10%) | |
| Gastrointestinal disorders | ||
| Enteritis | 1/10 (10%) | |
Other (Not Including Serious) Adverse Events |
||
| Ofatumumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | |
| Blood and lymphatic system disorders | ||
| Neutropenia | 4/10 (40%) | |
| Leukopenia | 3/10 (30%) | |
| Lymphopenia | 3/10 (30%) | |
| Anaemia | 2/10 (20%) | |
| Thrombocytopenia | 2/10 (20%) | |
| Iron deficiency anaemia | 1/10 (10%) | |
| Lymph node pain | 1/10 (10%) | |
| Cardiac disorders | ||
| Palpitations | 1/10 (10%) | |
| Ventricular extrasystoles | 1/10 (10%) | |
| Ventricular tachycardia | 1/10 (10%) | |
| Ear and labyrinth disorders | ||
| Vertigo positional | 2/10 (20%) | |
| Ear pain | 1/10 (10%) | |
| Tinnitus | 1/10 (10%) | |
| Eye disorders | ||
| Cataract | 1/10 (10%) | |
| Conjunctivitis allergic | 1/10 (10%) | |
| Gastrointestinal disorders | ||
| Constipation | 2/10 (20%) | |
| Diarrhoea | 2/10 (20%) | |
| Stomatitis | 2/10 (20%) | |
| Abdominal pain lower | 1/10 (10%) | |
| Colonic polyp | 1/10 (10%) | |
| Gastric ulcer | 1/10 (10%) | |
| Gastritis atrophic | 1/10 (10%) | |
| Gingival swelling | 1/10 (10%) | |
| General disorders | ||
| Fatigue | 2/10 (20%) | |
| Pyrexia | 2/10 (20%) | |
| Asthenia | 1/10 (10%) | |
| Chills | 1/10 (10%) | |
| Influenza like illness | 1/10 (10%) | |
| Mucosal erosion | 1/10 (10%) | |
| Oedema peripheral | 1/10 (10%) | |
| Hepatobiliary disorders | ||
| Hepatic function abnormal | 1/10 (10%) | |
| Infections and infestations | ||
| Nasopharyngitis | 3/10 (30%) | |
| Herpes zoster | 2/10 (20%) | |
| Influenza | 2/10 (20%) | |
| Gastroenteritis | 1/10 (10%) | |
| Oral herpes | 1/10 (10%) | |
| Pneumonia | 1/10 (10%) | |
| Upper respiratory tract infection | 1/10 (10%) | |
| Injury, poisoning and procedural complications | ||
| Infusion related reaction | 4/10 (40%) | |
| Procedural complication | 1/10 (10%) | |
| Thermal burn | 1/10 (10%) | |
| Investigations | ||
| Blood lactate dehydrogenase increased | 5/10 (50%) | |
| Lymphocyte count decreased | 3/10 (30%) | |
| White blood cell count decreased | 3/10 (30%) | |
| Aspartate aminotransferase increased | 2/10 (20%) | |
| Blood glucose increased | 2/10 (20%) | |
| Neutrophil count decreased | 2/10 (20%) | |
| Platelet count decreased | 2/10 (20%) | |
| Protein total decreased | 2/10 (20%) | |
| Alanine aminotransferase increased | 1/10 (10%) | |
| Blood albumin decreased | 1/10 (10%) | |
| Blood potassium decreased | 1/10 (10%) | |
| Blood potassium increased | 1/10 (10%) | |
| Blood urea increased | 1/10 (10%) | |
| Blood uric acid increased | 1/10 (10%) | |
| Electrocardiogram QT prolonged | 1/10 (10%) | |
| Gamma-glutamyltransferase increased | 1/10 (10%) | |
| Weight increased | 1/10 (10%) | |
| Metabolism and nutrition disorders | ||
| Hyperglycaemia | 2/10 (20%) | |
| Decreased appetite | 1/10 (10%) | |
| Electrolyte imbalance | 1/10 (10%) | |
| Hypoglycaemia | 1/10 (10%) | |
| Tumour lysis syndrome | 1/10 (10%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthritis | 1/10 (10%) | |
| Back pain | 1/10 (10%) | |
| Muscular weakness | 1/10 (10%) | |
| Musculoskeletal pain | 1/10 (10%) | |
| Osteoarthritis | 1/10 (10%) | |
| Nervous system disorders | ||
| Peripheral sensory neuropathy | 3/10 (30%) | |
| Burning sensation | 1/10 (10%) | |
| Dizziness | 1/10 (10%) | |
| Dysaesthesia | 1/10 (10%) | |
| Dysgeusia | 1/10 (10%) | |
| Headache | 1/10 (10%) | |
| Hypoaesthesia | 1/10 (10%) | |
| Tremor | 1/10 (10%) | |
| Psychiatric disorders | ||
| Insomnia | 1/10 (10%) | |
| Renal and urinary disorders | ||
| Dysuria | 1/10 (10%) | |
| Pollakiuria | 1/10 (10%) | |
| Renal impairment | 1/10 (10%) | |
| Reproductive system and breast disorders | ||
| Vaginal haemorrhage | 1/10 (10%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 1/10 (10%) | |
| Dyspnoea exertional | 1/10 (10%) | |
| Pleural effusion | 1/10 (10%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash | 5/10 (50%) | |
| Eczema | 2/10 (20%) | |
| Rash pruritic | 1/10 (10%) | |
| Vascular disorders | ||
| Hypotension | 1/10 (10%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
- 112758