Leukaemia, Lymphocytic, Chronic
Conditions
Keywords
B-cell, cyclophosphamide, fludarabine, Chronic Lymphocytic Leukemia, Ofatumumab
Brief summary
To investigate the safety and efficacy of two dose regimes of ofatumumab in combination with chemotherapy in previously untreated patients with B-CLL
Interventions
DRUGOfatumumab 500mg
Ofatumumab 500mg or should be diluted into 1000mL pyrogenefree saline and administered as an IV infusion.Duration of infusion will be approximately 6½ hours.Infusions should be given every 4 weeks until a total of 6 infusions has been given.
DRUGOfatumumab 1000mg
Ofatumumab 1000mg or should be diluted into 1000mL pyrogenefree saline and administered as an IV infusion.Duration of infusion will be approximately 6½ hours.Infusions should be given every 4 weeks until a total of 6 infusions has been given.
DRUGFludarabine
Fludarabine (25 mg/m2) should be administered as an IV infusion daily, Days 2 through 4 of Course 1, and Days 1 through 3 of Courses 2 through 6, every 4 weeks for 6 courses
DRUGCyclophosphamide
Cyclophosphamide (250 mg/m2) should be administered as an IV infusion daily, Days 2 through 4 of Course 1, and Days 1 through 3 of Courses 2 through 6, every 4 weeks for 6 courses.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with active B-CLL and with an indication for treatment 2. Age ≥ 18 years 3. Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out
Exclusion criteria
1. Any previous treatment for B-CLL or any other treatments that can be considered active against B-CLL 2. Glucocorticoid unless given in doses ≤ 10 mg /day for other indications than B-CLL (e.g. asthma) 3. Known transformation of B-CLL 4. Known CNS involvement of B-CLL 5. Past or current malignancy, except for: 1. Cervical carcinoma Stage 1B or less 2. Non-invasive basal cell and squamous cell skin carcinoma 3. Malignant melanoma with a complete response of a duration of \> 10 years 4. Other cancer diagnoses with a complete response of a duration of \> 5 years 6. Chronic or current infectious disease requiring systemic treatment 7. Clinically significant cardiac disease 8. Significant concurrent, uncontrolled medical condition 9. History of significant cerebrovascular disease 10. Known HIV positive 11. Positive serology for hepatitis B, unless due to vaccination 12. Leukapheresis, except as a safety measure before chemotherapy 13. ECOG Performance Status of 3 or 4 14. Patients who at the time of inclusion are not expected to be able to complete the ofatumumab-FC regimen 15. Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 1 16. Current participation in any other interventional clinical study 17. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 18. Breast feeding women or women with a positive pregnancy test at Visit 1 19. Women of childbearing potential not willing to use adequate contraception for up to one year after last dose of ofatumumab. Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the USA the use of a double barrier method is also considered adequate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Par.) With Complete Remission (CR), Measured From Start of Treatment Until 3 Months After Last Infusion | Start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32) | Par. were evaluated for response by an Independent Endpoint Review Committee (IRC) in accordance with the National Cancer Institute-sponsored Working Group (NCI-WG) 1996 guideline. Par. with Complete Remission (CR) were classified as complete responders. As per NCI-WG, CR requires all of the following criteria for a period of \>=2 months: absence of lymphadenopathy (all lymph nodes \<1.0 centimeters), no hepatomegaly/splenomegaly, absence of constitutional symptoms, lymphocytes \<=4.0\*10\^9/liter (L), neutrophil leukocytes \>=1.5\*10\^9/L, platelets \>100\*10\^9/L, and hemoglobin \>11 grams/deciliter. |
| Number of Participants (Par.) Who Were Classified as Responders and Non-responders | From start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32) | Par. were evaluated by an IRC in accordance with NCI-WG 1996 guideline. Responders: CR, Nodular Partial Remission (nPR, same as CR, but persistent bone marrow nodules), and Partial Remission (PR, \>=50% decrease in lymphocytes from pretreatment baseline (BL) value, \>=50% reduction in lymphadenopathy, \>=50% reduction of liver/spleen and neutrophils \>= 1.5\*10\^9/L or platelets \>100\*10\^9/L or hemoglobin \>11 g/dL (or 50% improvement over BL for neutrophils, platelets, hemoglobin); non-responders: Stable Disease (SD, did not achieve CR/PR, and no PD), Progressive Disease (PD), or Not Evaluable (NE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Next Anti-chronic Lymphocytic Leukemia (CLL) Therapy or Death | From time of randomization to first administration of next anti-CLL therapy other than ofatumumab or death, assessed over 5 years | Time to next anti-CLL (anti-lymphoma) therapy was defined as the time from randomization until the time of first administration of the next anti-lymphoma therapy other than ofatumumab or death. For participants who were lost to follow-up, the time was censored at the date of the last attended visit at which the endpoint was assessed. |
| Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Baseline Visit 2 (Week [Wk] 0); Visits 9 (Wk 4), 21 (Wk 12), 25 (Wk 16), 29 (Wk 20), 33 (Month [M] 1 after start of last infusion [LI]), 34 (M 3 after start of LI), 35 (M 6 after start of LI), 36 (M 9 after start of LI), and 37 (M 12 after start of L | Tumor size was measured by physical examination of palpable abnormal lymph nodes. Percent change from Baseline (Visit 2, Week 0) = (value at indicated visits minus value at Visit 2 divided by value at Visit 2) \* 100. Visits 33, 34, 35, 36, and 37 are measured in the number of months from the start of the last infusion. The start of the last infusion could have occurred up to Week 20. |
| Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | Baseline Visit 2 (Week [Wk] 0); Visits 15 (Wk 8), 21 (Wk 12), 25 (Wk 16), 29 (Wk 20), 33 (Month [M] 1 after start of last infusion [LI]), 34 (M 3 after start of LI) | Malignant B cells (CD5+CD19+ and CD5+CD20+) were measured in peripheral blood samples by flow cytometry. Percent change from Screening (Visit 1, Week -2) = (value at indicated visits minus value at Visit 1 divided by value at Visit 1) \* 100. Visits 33 and 34 are measured in the number of months from the start of the last infusion. The start of the last infusion could have occurred up to Week 20. |
| Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 43 (Month 60) | From first treatment (Visit 2) up to Visit 43 (Month 60) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. A list of AEs experienced in the study at a frequency threshold of 5% can be found in the AE section. |
| Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visits 1 (Screening, Visit -2), 21 (Week 12), 35 (Month 6), and 39 (Month 18) | HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 21, 35, and 39 for analysis of HAHA. Analysis of HAHA was done in batches. |
| Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | From first treatment (Visit 2) up to Visit 43 (Month 60) | Myelosuppression is one of the expected AEs for FC treatment and is defined as the decrease in the ability of the bone marrow to produce blood cells. The number of participants with myelosuppression was assessed from laboratory measurements with Grades 3(severe)-4 (life-threatening/disabling) (1, mild; 2, moderate; 5, death) according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. The CTCAE is issued by the National Cancer Institute (NCI) and is the standard classification used for the severity grading scale for AEs in cancer therapy clinical studies. |
| Percent Change From Screening (Visit 1) in Complement (CH50) Levels at Visit 9 (Week 4) | Visit 1 (Week -2) and Visit 9 (Week 4) | Blood samples were drawn from participants at Visits 1 and 9 for analysis of complement (CH50) levels. Analysis of CH50 was done in batches, and CH50 levels were measured two hours after the end of study medication infusion. Percent change from Screening (Visit 1, Week -2) = (value at Visit 9 minus value at Visit 1 divided by value at Visit 1) \* 100. |
| Duration of Response | From time of initial response to disease progression or death, whichever came first, assessed over 2 years | The duration of response was defined as the time from the initial response (the first visit at which response was observed) to progression or death. For participants who were lost to follow-up, duration of response was censored at the date of the last attended visit at which the endpoint was assessed. |
| Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose) | Cmax is defined as the maximum concentration of drug in plasma samples. Ctrough is defined as the trough plasma concentration (measured concentration at the end of a dosing interval \[taken directly before next administration\]). No drug is present before the first infusion; therefore, there are no Ctrough results for the first infusion. |
| AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose) | AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-672) is AUC from start of infusion to 672 hours after start of infusion; AUC(0-inf) is AUC from start of infusion extrapolated to infinity. |
| t1/2 After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose) | t1/2 is defined as terminal half-life and is the time required for the amount of drug in the body to decrease by half. |
| CL After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose) | CL is the clearance of drug from plasma, which is defined as the volume of plasma from which the drug is cleared per unit time. |
| Vss After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose) | Vss is defined as the volume of distribution at steady state of ofatumumab. |
| Number of Participants With Progression or Death | From time of randomization to first documented evidence of disease progression or death due to any cause, whichever came first, assessed over 2 years | Disease progression is characterized by at least one of the following, per the Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia: a \>=50% increase in the sum of the products of at least two lymph nodes on two consecutive determinations 2 weeks apart (at least one node must be \>=2 centimeters); or the appearance of new palpable lymph nodes; or a \>=50% increase in liver and/or spleen size (measurement below the costal margin); or the appearance of palpable hepatomegaly or splenomegaly not previously present; or a \>=50% increase in the numbers of circulating lymphocytes to at least 5.0 \* 10\^9/Liter; or transformation to a more aggressive histology (e.g., Richter's syndrome or prolymphocytic leukemia with \>55% prolymphocytes). For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS. |
| Number of Participants Classified as Responders Having CR Who Tested Negative for Minimal Residual Disease (MRD) | From start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to course 6 or Week 32) | MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells (CD5+CD19+) to determine if there was any MRD. |
| Progression-Free Survival | From time of randomization to first documented evidence of disease progression or death due to any cause, whichever came first, assessed over 2 years | Progression-free survival (PFS) was defined as the time from randomization until the first radiologically or clinically documented evidence of progression or death due to any cause, if sooner. For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS. |
Countries
United Kingdom, United States
Participant flow
Pre-assignment details
Participants received up to 6 courses (22 weeks) of treatment. After treatment, participants were evaluated for up to 18 months in a follow-up (FU) period and then entered an extended FU phase (up to Month 60). The overall study period reported is from 09 January 2007 to 05 June 2013, when all phases of the study were completed.
Participants by arm
| Arm | Count |
|---|---|
| Ofatumumab 500 mg + FC Ofatumumab iv infusion initiated at 300 mg for course 1, followed by dose of 500 mg for courses 2-6 in combination with fludarabine iv (25 mg/m\^2 daily on Days 1-3) and cyclophosphamide iv (250 mg/m\^2 daily on Days 1-3) administered every 4 weeks for a total of 6 courses | 31 |
| Ofatumumab 1000 mg + FC Ofatumumab iv infusion initiated at 300 mg for course 1, followed by dose of 1000 mg for courses 2-6 in combination with fludarabine iv (25 mg/m\^2 daily on Days 1-3) and cyclophosphamide iv (250 mg/m\^2 daily on Days 1-3) administered every 4 weeks for a total of 6 courses | 30 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extended Follow-up (FU) Phase (2-5 Years | Death | 1 | 1 |
| Extended Follow-up (FU) Phase (2-5 Years | Lost to Follow-up | 3 | 1 |
| Extended Follow-up (FU) Phase (2-5 Years | Medical Reasons | 1 | 0 |
| Extended Follow-up (FU) Phase (2-5 Years | New Anti-CLL Treatment | 4 | 8 |
| Extended Follow-up (FU) Phase (2-5 Years | Secondary Acute Myeloid Leukemia | 1 | 0 |
| Treatment and Follow-up Phase (2 Years) | Adverse Event | 4 | 2 |
| Treatment and Follow-up Phase (2 Years) | Death | 1 | 1 |
| Treatment and Follow-up Phase (2 Years) | Investigator Decision | 0 | 1 |
| Treatment and Follow-up Phase (2 Years) | Lack of Efficacy | 0 | 4 |
| Treatment and Follow-up Phase (2 Years) | Participant Had Bone Marrow Transplant | 1 | 0 |
| Treatment and Follow-up Phase (2 Years) | Participant Had No Response | 2 | 1 |
| Treatment and Follow-up Phase (2 Years) | Participant Had Stable Disease | 1 | 0 |
| Treatment and Follow-up Phase (2 Years) | Participant Received New Therapy | 1 | 1 |
| Treatment and Follow-up Phase (2 Years) | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC | Total |
|---|---|---|---|
| Age, Continuous | 56.1 Years STANDARD_DEVIATION 8.4 | 56.4 Years STANDARD_DEVIATION 8.7 | 56.2 Years STANDARD_DEVIATION 8.5 |
| Race/Ethnicity, Customized Black or African American | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 31 participants | 29 participants | 60 participants |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 20 Participants | 23 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 31 | 30 / 30 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 17 / 31 | 23 / 30 | 7 / 31 | 5 / 30 |
Outcome results
Primary
Number of Participants (Par.) Who Were Classified as Responders and Non-responders
Par. were evaluated by an IRC in accordance with NCI-WG 1996 guideline. Responders: CR, Nodular Partial Remission (nPR, same as CR, but persistent bone marrow nodules), and Partial Remission (PR, \>=50% decrease in lymphocytes from pretreatment baseline (BL) value, \>=50% reduction in lymphadenopathy, \>=50% reduction of liver/spleen and neutrophils \>= 1.5\*10\^9/L or platelets \>100\*10\^9/L or hemoglobin \>11 g/dL (or 50% improvement over BL for neutrophils, platelets, hemoglobin); non-responders: Stable Disease (SD, did not achieve CR/PR, and no PD), Progressive Disease (PD), or Not Evaluable (NE).
Time frame: From start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ofatumumab 500 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | All responders | 24 participants |
| Ofatumumab 500 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Responders, CR | 10 participants |
| Ofatumumab 500 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Responders, nPR | 1 participants |
| Ofatumumab 500 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Responders, PR | 13 participants |
| Ofatumumab 500 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | All Non-responders | 7 participants |
| Ofatumumab 500 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Non-responders, SD | 3 participants |
| Ofatumumab 500 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Non-responders, PD | 2 participants |
| Ofatumumab 500 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Non-responders, NE | 2 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Non-responders, NE | 1 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | All responders | 22 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | All Non-responders | 8 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Responders, CR | 15 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Non-responders, PD | 5 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Responders, nPR | 1 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Non-responders, SD | 2 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) Who Were Classified as Responders and Non-responders | Responders, PR | 6 participants |
Primary
Number of Participants (Par.) With Complete Remission (CR), Measured From Start of Treatment Until 3 Months After Last Infusion
Par. were evaluated for response by an Independent Endpoint Review Committee (IRC) in accordance with the National Cancer Institute-sponsored Working Group (NCI-WG) 1996 guideline. Par. with Complete Remission (CR) were classified as complete responders. As per NCI-WG, CR requires all of the following criteria for a period of \>=2 months: absence of lymphadenopathy (all lymph nodes \<1.0 centimeters), no hepatomegaly/splenomegaly, absence of constitutional symptoms, lymphocytes \<=4.0\*10\^9/liter (L), neutrophil leukocytes \>=1.5\*10\^9/L, platelets \>100\*10\^9/L, and hemoglobin \>11 grams/deciliter.
Time frame: Start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32)
Population: Full Analysis Set (FAS): all participants who had been exposed to study drug irrespective of their compliance to the planned course of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab 500 mg + FC | Number of Participants (Par.) With Complete Remission (CR), Measured From Start of Treatment Until 3 Months After Last Infusion | 10 participants |
| Ofatumumab 1000 mg + FC | Number of Participants (Par.) With Complete Remission (CR), Measured From Start of Treatment Until 3 Months After Last Infusion | 15 participants |
Secondary
AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)
AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-672) is AUC from start of infusion to 672 hours after start of infusion; AUC(0-inf) is AUC from start of infusion extrapolated to infinity.
Time frame: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)
Population: FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab 500 mg + FC | AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, AUC(0-inf), n=24, 26 | 2453 Milligrams * hour per liter (mg.h/L) | Geometric Coefficient of Variation 1.28 |
| Ofatumumab 500 mg + FC | AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, AUC(0-672), n=24, 26 | 2452 Milligrams * hour per liter (mg.h/L) | Geometric Coefficient of Variation 1.28 |
| Ofatumumab 500 mg + FC | AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, AUC(0-inf), n=16, 16 | 145236 Milligrams * hour per liter (mg.h/L) | Geometric Coefficient of Variation 0.54 |
| Ofatumumab 500 mg + FC | AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, AUC(0-672), n=20, 19 | 74728 Milligrams * hour per liter (mg.h/L) | Geometric Coefficient of Variation 0.39 |
| Ofatumumab 1000 mg + FC | AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, AUC(0-672), n=20, 19 | 149019 Milligrams * hour per liter (mg.h/L) | Geometric Coefficient of Variation 0.75 |
| Ofatumumab 1000 mg + FC | AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, AUC(0-inf), n=24, 26 | 1915 Milligrams * hour per liter (mg.h/L) | Geometric Coefficient of Variation 0.74 |
| Ofatumumab 1000 mg + FC | AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, AUC(0-inf), n=16, 16 | 397577 Milligrams * hour per liter (mg.h/L) | Geometric Coefficient of Variation 0.35 |
| Ofatumumab 1000 mg + FC | AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, AUC(0-672), n=24, 26 | 1915 Milligrams * hour per liter (mg.h/L) | Geometric Coefficient of Variation 0.74 |
Secondary
CL After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)
CL is the clearance of drug from plasma, which is defined as the volume of plasma from which the drug is cleared per unit time.
Time frame: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)
Population: FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab 500 mg + FC | CL After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, CL, n=24, 26 | 122 Milliliters per hour (mL/h) | Geometric Coefficient of Variation 1.28 |
| Ofatumumab 500 mg + FC | CL After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, CL, n=20, 19 | 6.7 Milliliters per hour (mL/h) | Geometric Coefficient of Variation 0.39 |
| Ofatumumab 1000 mg + FC | CL After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, CL, n=24, 26 | 157 Milliliters per hour (mL/h) | Geometric Coefficient of Variation 0.74 |
| Ofatumumab 1000 mg + FC | CL After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, CL, n=20, 19 | 6.7 Milliliters per hour (mL/h) | Geometric Coefficient of Variation 0.75 |
Secondary
Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)
Cmax is defined as the maximum concentration of drug in plasma samples. Ctrough is defined as the trough plasma concentration (measured concentration at the end of a dosing interval \[taken directly before next administration\]). No drug is present before the first infusion; therefore, there are no Ctrough results for the first infusion.
Time frame: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)
Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab 500 mg + FC | Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, Cmax, n=31, 29 | 67.5 Milligrams per liter (mg/L) | Geometric Coefficient of Variation 0.47 |
| Ofatumumab 500 mg + FC | Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, Cmax, n=22, 19 | 201 Milligrams per liter (mg/L) | Geometric Coefficient of Variation 0.3 |
| Ofatumumab 500 mg + FC | Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, Ctrough, n=22, 19 | 19.9 Milligrams per liter (mg/L) | Geometric Coefficient of Variation 12.69 |
| Ofatumumab 1000 mg + FC | Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, Cmax, n=31, 29 | 57.2 Milligrams per liter (mg/L) | Geometric Coefficient of Variation 0.47 |
| Ofatumumab 1000 mg + FC | Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, Cmax, n=22, 19 | 427 Milligrams per liter (mg/L) | Geometric Coefficient of Variation 0.34 |
| Ofatumumab 1000 mg + FC | Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, Ctrough, n=22, 19 | 62.2 Milligrams per liter (mg/L) | Geometric Coefficient of Variation 10.36 |
Secondary
Duration of Response
The duration of response was defined as the time from the initial response (the first visit at which response was observed) to progression or death. For participants who were lost to follow-up, duration of response was censored at the date of the last attended visit at which the endpoint was assessed.
Time frame: From time of initial response to disease progression or death, whichever came first, assessed over 2 years
Population: FAS. Only those participants classified as responders were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab 500 mg + FC | Duration of Response | NA months |
| Ofatumumab 1000 mg + FC | Duration of Response | NA months |
Secondary
Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening
Malignant B cells (CD5+CD19+ and CD5+CD20+) were measured in peripheral blood samples by flow cytometry. Percent change from Screening (Visit 1, Week -2) = (value at indicated visits minus value at Visit 1 divided by value at Visit 1) \* 100. Visits 33 and 34 are measured in the number of months from the start of the last infusion. The start of the last infusion could have occurred up to Week 20.
Time frame: Baseline Visit 2 (Week [Wk] 0); Visits 15 (Wk 8), 21 (Wk 12), 25 (Wk 16), 29 (Wk 20), 33 (Month [M] 1 after start of last infusion [LI]), 34 (M 3 after start of LI)
Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 15 (Wk 8), n=25, 26 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 25 (Wk16), n=23, 21 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 21 (Wk 12), n=24, 24 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 29 (Wk 20), n=22, 19 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 25 (Wk16), n=23, 21 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 33 (Wk 24), n=21, 24 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 29 (Wk 20), n=22, 19 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 21 (Wk 12), n=24, 24 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 33 (Wk 24), n=21, 24 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 34 (Wk 32), n=20, 22 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 34 (Wk 32), n=20, 22 | -100.00 percent change in cells |
| Ofatumumab 500 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 15 (Wk 8), n=25, 26 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 34 (Wk 32), n=20, 22 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 15 (Wk 8), n=25, 26 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 21 (Wk 12), n=24, 24 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 29 (Wk 20), n=22, 19 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 33 (Wk 24), n=21, 24 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 34 (Wk 32), n=20, 22 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 15 (Wk 8), n=25, 26 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 21 (Wk 12), n=24, 24 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 25 (Wk16), n=23, 21 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 29 (Wk 20), n=22, 19 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD20+ cells, Visit 33 (Wk 24), n=21, 24 | -100.00 percent change in cells |
| Ofatumumab 1000 mg + FC | Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening | CD5+CD19+ cells, Visit 25 (Wk16), n=23, 21 | -100.00 percent change in cells |
Secondary
Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37
Tumor size was measured by physical examination of palpable abnormal lymph nodes. Percent change from Baseline (Visit 2, Week 0) = (value at indicated visits minus value at Visit 2 divided by value at Visit 2) \* 100. Visits 33, 34, 35, 36, and 37 are measured in the number of months from the start of the last infusion. The start of the last infusion could have occurred up to Week 20.
Time frame: Baseline Visit 2 (Week [Wk] 0); Visits 9 (Wk 4), 21 (Wk 12), 25 (Wk 16), 29 (Wk 20), 33 (Month [M] 1 after start of last infusion [LI]), 34 (M 3 after start of LI), 35 (M 6 after start of LI), 36 (M 9 after start of LI), and 37 (M 12 after start of L
Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 21 (Week 12), n=24, 23 | -100.00 percent change in tumor size |
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 34 (Month 3), n=22, 23 | -100.00 percent change in tumor size |
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 29 (Week 20), n=22, 16 | -100.00 percent change in tumor size |
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 35 (Month 6), n=19, 22 | -100.00 percent change in tumor size |
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 25 (Week 16), n=23, 20 | -100.00 percent change in tumor size |
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 36 (Month 9), n=20, 22 | -100.00 percent change in tumor size |
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 33 (Month 1), n=21, 24 | -100.00 percent change in tumor size |
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 37 (Month 12), n=20, 18 | -100.00 percent change in tumor size |
| Ofatumumab 500 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 9 (Week 4), n=29, 28 | -75.00 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 37 (Month 12), n=20, 18 | -100.00 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 9 (Week 4), n=29, 28 | -70.90 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 21 (Week 12), n=24, 23 | -100.00 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 25 (Week 16), n=23, 20 | -100.00 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 29 (Week 20), n=22, 16 | -100.00 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 33 (Month 1), n=21, 24 | -100.00 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 34 (Month 3), n=22, 23 | -100.00 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 35 (Month 6), n=19, 22 | -100.00 percent change in tumor size |
| Ofatumumab 1000 mg + FC | Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37 | Visit 36 (Month 9), n=20, 22 | -100.00 percent change in tumor size |
Secondary
Number of Participants Classified as Responders Having CR Who Tested Negative for Minimal Residual Disease (MRD)
MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells (CD5+CD19+) to determine if there was any MRD.
Time frame: From start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to course 6 or Week 32)
Population: FAS. Only participants with CR at Visit 34 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab 500 mg + FC | Number of Participants Classified as Responders Having CR Who Tested Negative for Minimal Residual Disease (MRD) | 2 participants |
| Ofatumumab 1000 mg + FC | Number of Participants Classified as Responders Having CR Who Tested Negative for Minimal Residual Disease (MRD) | 6 participants |
Secondary
Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 43 (Month 60)
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. A list of AEs experienced in the study at a frequency threshold of 5% can be found in the AE section.
Time frame: From first treatment (Visit 2) up to Visit 43 (Month 60)
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab 500 mg + FC | Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 43 (Month 60) | 31 participants |
| Ofatumumab 1000 mg + FC | Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 43 (Month 60) | 30 participants |
Secondary
Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia)
Myelosuppression is one of the expected AEs for FC treatment and is defined as the decrease in the ability of the bone marrow to produce blood cells. The number of participants with myelosuppression was assessed from laboratory measurements with Grades 3(severe)-4 (life-threatening/disabling) (1, mild; 2, moderate; 5, death) according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. The CTCAE is issued by the National Cancer Institute (NCI) and is the standard classification used for the severity grading scale for AEs in cancer therapy clinical studies.
Time frame: From first treatment (Visit 2) up to Visit 43 (Month 60)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ofatumumab 500 mg + FC | Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | Anemia | 6 participants |
| Ofatumumab 500 mg + FC | Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | Leukopenia | 23 participants |
| Ofatumumab 500 mg + FC | Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | Neutropenia | 29 participants |
| Ofatumumab 500 mg + FC | Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | Thrombocytopenia | 4 participants |
| Ofatumumab 1000 mg + FC | Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | Thrombocytopenia | 8 participants |
| Ofatumumab 1000 mg + FC | Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | Anemia | 8 participants |
| Ofatumumab 1000 mg + FC | Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | Neutropenia | 26 participants |
| Ofatumumab 1000 mg + FC | Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia) | Leukopenia | 22 participants |
Secondary
Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39
HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 21, 35, and 39 for analysis of HAHA. Analysis of HAHA was done in batches.
Time frame: Visits 1 (Screening, Visit -2), 21 (Week 12), 35 (Month 6), and 39 (Month 18)
Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ofatumumab 500 mg + FC | Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visit 1 (Week -2), n=31, 30 | 0 participants |
| Ofatumumab 500 mg + FC | Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visit 21 (Week 12), n=24, 24 | 0 participants |
| Ofatumumab 500 mg + FC | Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visit 35 (Month 6), n=19, 22 | 0 participants |
| Ofatumumab 500 mg + FC | Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visit 39 (Month 18), n=14, 13 | 0 participants |
| Ofatumumab 1000 mg + FC | Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visit 39 (Month 18), n=14, 13 | 0 participants |
| Ofatumumab 1000 mg + FC | Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visit 1 (Week -2), n=31, 30 | 0 participants |
| Ofatumumab 1000 mg + FC | Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visit 35 (Month 6), n=19, 22 | 0 participants |
| Ofatumumab 1000 mg + FC | Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39 | Visit 21 (Week 12), n=24, 24 | 0 participants |
Secondary
Number of Participants With Progression or Death
Disease progression is characterized by at least one of the following, per the Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia: a \>=50% increase in the sum of the products of at least two lymph nodes on two consecutive determinations 2 weeks apart (at least one node must be \>=2 centimeters); or the appearance of new palpable lymph nodes; or a \>=50% increase in liver and/or spleen size (measurement below the costal margin); or the appearance of palpable hepatomegaly or splenomegaly not previously present; or a \>=50% increase in the numbers of circulating lymphocytes to at least 5.0 \* 10\^9/Liter; or transformation to a more aggressive histology (e.g., Richter's syndrome or prolymphocytic leukemia with \>55% prolymphocytes). For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.
Time frame: From time of randomization to first documented evidence of disease progression or death due to any cause, whichever came first, assessed over 2 years
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab 500 mg + FC | Number of Participants With Progression or Death | 3 Participants |
| Ofatumumab 1000 mg + FC | Number of Participants With Progression or Death | 7 Participants |
Secondary
Percent Change From Screening (Visit 1) in Complement (CH50) Levels at Visit 9 (Week 4)
Blood samples were drawn from participants at Visits 1 and 9 for analysis of complement (CH50) levels. Analysis of CH50 was done in batches, and CH50 levels were measured two hours after the end of study medication infusion. Percent change from Screening (Visit 1, Week -2) = (value at Visit 9 minus value at Visit 1 divided by value at Visit 1) \* 100.
Time frame: Visit 1 (Week -2) and Visit 9 (Week 4)
Population: FAS. Data were provided for the number of participants attending Visit 9. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab 500 mg + FC | Percent Change From Screening (Visit 1) in Complement (CH50) Levels at Visit 9 (Week 4) | 0 Percent change in complement levels |
| Ofatumumab 1000 mg + FC | Percent Change From Screening (Visit 1) in Complement (CH50) Levels at Visit 9 (Week 4) | 0 Percent change in complement levels |
Secondary
Progression-Free Survival
Progression-free survival (PFS) was defined as the time from randomization until the first radiologically or clinically documented evidence of progression or death due to any cause, if sooner. For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.
Time frame: From time of randomization to first documented evidence of disease progression or death due to any cause, whichever came first, assessed over 2 years
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab 500 mg + FC | Progression-Free Survival | NA months |
| Ofatumumab 1000 mg + FC | Progression-Free Survival | 23.5 months |
Secondary
t1/2 After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)
t1/2 is defined as terminal half-life and is the time required for the amount of drug in the body to decrease by half.
Time frame: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)
Population: FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab 500 mg + FC | t1/2 After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, t1/2, n=24, 26 | 19.4 hours | Geometric Coefficient of Variation 1.13 |
| Ofatumumab 500 mg + FC | t1/2 After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, t1/2, n=16, 16 | 551 hours | Geometric Coefficient of Variation 0.31 |
| Ofatumumab 1000 mg + FC | t1/2 After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, t1/2, n=24, 26 | 18.8 hours | Geometric Coefficient of Variation 0.62 |
| Ofatumumab 1000 mg + FC | t1/2 After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, t1/2, n=16, 16 | 746 hours | Geometric Coefficient of Variation 0.3 |
Secondary
Time to Next Anti-chronic Lymphocytic Leukemia (CLL) Therapy or Death
Time to next anti-CLL (anti-lymphoma) therapy was defined as the time from randomization until the time of first administration of the next anti-lymphoma therapy other than ofatumumab or death. For participants who were lost to follow-up, the time was censored at the date of the last attended visit at which the endpoint was assessed.
Time frame: From time of randomization to first administration of next anti-CLL therapy other than ofatumumab or death, assessed over 5 years
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab 500 mg + FC | Time to Next Anti-chronic Lymphocytic Leukemia (CLL) Therapy or Death | 33.4 months |
| Ofatumumab 1000 mg + FC | Time to Next Anti-chronic Lymphocytic Leukemia (CLL) Therapy or Death | 33.3 months |
Secondary
Vss After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)
Vss is defined as the volume of distribution at steady state of ofatumumab.
Time frame: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)
Population: FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ofatumumab 500 mg + FC | Vss After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, Vss, n=24, 26 | 3.88 liters | Geometric Coefficient of Variation 0.37 |
| Ofatumumab 500 mg + FC | Vss After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, Vss, n=16, 16 | 5.15 liters | Geometric Coefficient of Variation 0.27 |
| Ofatumumab 1000 mg + FC | Vss After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | First infusion, Vss, n=24, 26 | 4.57 liters | Geometric Coefficient of Variation 0.3 |
| Ofatumumab 1000 mg + FC | Vss After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20) | Sixth infusion, Vss, n=16, 16 | 5.77 liters | Geometric Coefficient of Variation 0.38 |