A Phase 2 interventional study of Ofatumumab 500mg and Ofatumumab 1000mg in Leukaemia, Lymphocytic, Chronic, sponsored by GlaxoSmithKline. Completed at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-02-10.
Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment
To investigate the safety and efficacy of two dose regimes of ofatumumab in combination with chemotherapy in previously untreated patients with B-CLL
1,780 studies on the registry are indexed under Leukemia, Lymphoid; 176 are open to participants now.
This study's enrollment of 61 is above the median of 36 across 1,416 interventional studies indexed under Leukemia, Lymphoid.
Browse Leukemia, Lymphoid studies →GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Past or current malignancy, except for:
Each patient will receive a total of 6 infusions with ofatumumab every 4 weeks in combination with fludarabine and cyclophosphamide. The first infusion will be 300mg followed by 5 infusions of 500mg
Drug: Ofatumumab 500mg · Drug: Fludarabine · Drug: Cyclophosphamide
Each patient will receive a total of 6 monthly infusions with ofatumumab in combination with fludarabine and cyclophosphamide. The first infusion will be 300mg followed by 5 infusions of 1000mg
Drug: Ofatumumab 1000mg · Drug: Fludarabine · Drug: Cyclophosphamide
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.
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.
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
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.
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)
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)
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
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
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
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
| Milestone | Ofatumumab 500 mg + Fludarabine and Cyclophosphamide (FC) | Ofatumumab 1000 mg + FC |
|---|---|---|
| Started | 31 | 30 |
| Completed | 19 | 19 |
| Not completed | 12 | 11 |
| Withdrew: Adverse event | 4 | 2 |
| Withdrew: Death | 1 | 1 |
| Withdrew: Withdrawal by subject | 2 | 1 |
| Withdrew: Lack of efficacy | 0 | 4 |
| Withdrew: Participant had no response | 2 | 1 |
| Withdrew: Participant had stable disease | 1 | 0 |
| Withdrew: Participant received new therapy | 1 | 1 |
| Withdrew: Participant had bone marrow transplant | 1 | 0 |
| Withdrew: Investigator decision | 0 | 1 |
| Milestone | Ofatumumab 500 mg + Fludarabine and Cyclophosphamide (FC) | Ofatumumab 1000 mg + FC |
|---|---|---|
| Started | 20 | 21 |
| Completed | 10 | 11 |
| Not completed | 10 | 10 |
| Withdrew: Lost to follow-up | 3 | 1 |
| Withdrew: Death | 1 | 1 |
| Withdrew: Medical reasons | 1 | 0 |
| Withdrew: New anti-cll treatment | 4 | 8 |
| Withdrew: Secondary acute myeloid leukemia | 1 | 0 |
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.
| participants | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Number of Participants (Par.) With Complete Remission (CR), Measured From Start of Treatment Until 3 Months After Last Infusion | 10 | 15 |
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.
| months | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Duration of Response | NA (NA to NA) | NA (NA to NA) |
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.
| months | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Progression-Free Survival | NA (NA to NA) | 23.5 (NA to NA) |
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.
| months | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Time to Next Anti-chronic Lymphocytic Leukemia (CLL) Therapy or Death | 33.4 (27.3 to 46.9) | 33.3 (26.7 to 54.6) |
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.
| percent change in tumor size | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Visit 9 (Week 4), n=29, 28 | -75.00 (-100.00 to 0.00) | -70.90 (-100.00 to 73.00) |
| Visit 21 (Week 12), n=24, 23 | -100.00 (-100.00 to 0.00) | -100.00 (-100.00 to -39.00) |
| Visit 25 (Week 16), n=23, 20 | -100.00 (-100.00 to 0.00) | -100.00 (-100.00 to -85.00) |
| Visit 29 (Week 20), n=22, 16 | -100.00 (-100.00 to 0.00) | -100.00 (-100.00 to -92.00) |
| Visit 33 (Month 1), n=21, 24 | -100.00 (-100.00 to 0.00) | -100.00 (-100.00 to -4.00) |
| Visit 34 (Month 3), n=22, 23 | -100.00 (-100.00 to 0.00) | -100.00 (-100.00 to -40.00) |
| Visit 35 (Month 6), n=19, 22 | -100.00 (-100.00 to 0.00) | -100.00 (-100.00 to 12.00) |
| Visit 36 (Month 9), n=20, 22 | -100.00 (-100.00 to 0.00) | -100.00 (-100.00 to 28.00) |
| Visit 37 (Month 12), n=20, 18 | -100.00 (-100.00 to -100.00) | -100.00 (-100.00 to -69.00) |
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.
| percent change in cells | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| CD5+CD19+ cells, Visit 15 (Wk 8), n=25, 26 | -100.00 (-100.0 to 22.0) | -100.00 (-100.00 to -81) |
| CD5+CD19+ cells, Visit 21 (Wk 12), n=24, 24 | -100.00 (-100.00 to -84.00) | -100.00 (-100.00 to -90.00) |
| CD5+CD19+ cells, Visit 25 (Wk16), n=23, 21 | -100.00 (-100.00 to -93.00) | -100.00 (-100.00 to -96) |
| CD5+CD19+ cells, Visit 29 (Wk 20), n=22, 19 | -100.00 (-100.00 to -98) | -100.00 (-100.00 to -96) |
| CD5+CD19+ cells, Visit 33 (Wk 24), n=21, 24 | -100.00 (-100.00 to -99.00) | -100.00 (-100.00 to -73) |
| CD5+CD19+ cells, Visit 34 (Wk 32), n=20, 22 | -100.00 (-100.00 to -95) | -100.00 (-100.00 to -97) |
| CD5+CD20+ cells, Visit 15 (Wk 8), n=25, 26 | -100.00 (-100.00 to 22.00) | -100.00 (-100.00 to -92) |
| CD5+CD20+ cells, Visit 21 (Wk 12), n=24, 24 | -100.00 (-100.00 to -84) | -100.00 (-100.00 to -96) |
| CD5+CD20+ cells, Visit 25 (Wk16), n=23, 21 | -100.00 (-100.00 to -93) | -100.00 (-100.00 to -100) |
| CD5+CD20+ cells, Visit 29 (Wk 20), n=22, 19 | -100.00 (-100.00 to -99) | -100.00 (-100.00 to -100) |
| CD5+CD20+ cells, Visit 33 (Wk 24), n=21, 24 | -100.00 (-100.00 to -99) | -100.00 (-100.00 to -97.00) |
| CD5+CD20+ cells, Visit 34 (Wk 32), n=20, 22 | -100.00 (-100.00 to -96) | -100.00 (-100.00 to -97.0) |
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.
| participants | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 43 (Month 60) | 31 | 30 |
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.
| participants | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Visit 1 (Week -2), n=31, 30 | 0 | 0 |
| Visit 21 (Week 12), n=24, 24 | 0 | 0 |
| Visit 35 (Month 6), n=19, 22 | 0 | 0 |
| Visit 39 (Month 18), n=14, 13 | 0 | 0 |
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.
| participants | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Anemia | 6 | 8 |
| Leukopenia | 23 | 22 |
| Neutropenia | 29 | 26 |
| Thrombocytopenia | 4 | 8 |
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.
| Percent change in complement levels | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Percent Change From Screening (Visit 1) in Complement (CH50) Levels at Visit 9 (Week 4) | 0 (-54 to 520) | 0 (-83 to 430) |
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).
| participants | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| All responders | 24 | 22 |
| Responders, CR | 10 | 15 |
| Responders, nPR | 1 | 1 |
| Responders, PR | 13 | 6 |
| All Non-responders | 7 | 8 |
| Non-responders, SD | 3 | 2 |
| Non-responders, PD | 2 | 5 |
| Non-responders, NE | 2 | 1 |
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.
| participants | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Number of Participants Classified as Responders Having CR Who Tested Negative for Minimal Residual Disease (MRD) | 2 | 6 |
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.
| Milligrams per liter (mg/L) | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| First infusion, Cmax, n=31, 29 | 67.5 ± 0.47 | 57.2 ± 0.47 |
| Sixth infusion, Cmax, n=22, 19 | 201 ± 0.30 | 427 ± 0.34 |
| Sixth infusion, Ctrough, n=22, 19 | 19.9 ± 12.69 | 62.2 ± 10.36 |
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.
| Milligrams * hour per liter (mg.h/L) | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| First infusion, AUC(0-inf), n=24, 26 | 2453 ± 1.28 | 1915 ± 0.74 |
| First infusion, AUC(0-672), n=24, 26 | 2452 ± 1.28 | 1915 ± 0.74 |
| Sixth infusion, AUC(0-inf), n=16, 16 | 145236 ± 0.54 | 397577 ± 0.35 |
| Sixth infusion, AUC(0-672), n=20, 19 | 74728 ± 0.39 | 149019 ± 0.75 |
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.
| hours | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| First infusion, t1/2, n=24, 26 | 19.4 ± 1.13 | 18.8 ± 0.62 |
| Sixth infusion, t1/2, n=16, 16 | 551 ± 0.31 | 746 ± 0.30 |
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.
| Milliliters per hour (mL/h) | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| First infusion, CL, n=24, 26 | 122 ± 1.28 | 157 ± 0.74 |
| Sixth infusion, CL, n=20, 19 | 6.7 ± 0.39 | 6.7 ± 0.75 |
Vss is defined as the volume of distribution at steady state of ofatumumab.
| liters | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| First infusion, Vss, n=24, 26 | 3.88 ± 0.37 | 4.57 ± 0.30 |
| Sixth infusion, Vss, n=16, 16 | 5.15 ± 0.27 | 5.77 ± 0.38 |
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.
| Participants | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC |
|---|---|---|
| Number of Participants With Progression or Death | 3 | 7 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ofatumumab 500 mg + Fludarabine and Cyclophosphamide (FC) | — | 17/31 (54.8%) | 31/31 (100%) |
| Ofatumumab 1000 mg + FC | — | 23/30 (76.7%) | 30/30 (100%) |
| Ofatumumab 500 mg + FC: Extended Follow-up Phase | — | 7/31 (22.6%) | — |
| Ofatumumab 1000 mg + FC: Extended Follow-up Phase | — | 5/30 (16.7%) | — |
| Event | Ofatumumab 500 mg + Fludarabine and Cyclophosphamide (FC) | Ofatumumab 1000 mg + FC | Ofatumumab 500 mg + FC: Extended Follow-up Phase | Ofatumumab 1000 mg + FC: Extended Follow-up Phase |
|---|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 10/31 | 16/30 | 0/31 | 1/30 |
| LeukopeniaBlood and lymphatic system disorders | 3/31 | 7/30 | 0/31 | 0/30 |
| Febrile neutropeniaBlood and lymphatic system disorders | 4/31 | 3/30 | 0/31 | 0/30 |
| ThrombocytopeniaBlood and lymphatic system disorders | 2/31 | 3/30 | 0/31 | 0/30 |
| PyrexiaGeneral disorders | 3/31 | 0/30 | 0/31 | 0/30 |
| LymphopeniaBlood and lymphatic system disorders | 0/31 | 2/30 | 0/31 | 0/30 |
| SepsisInfections and infestations | 0/31 | 2/30 | 0/31 | 0/30 |
| PneumoniaInfections and infestations | 2/31 | 2/30 | 0/31 | 1/30 |
| Myocardial infarctionCardiac disorders | 2/31 | 0/30 | 0/31 | 0/30 |
| AnaemiaBlood and lymphatic system disorders | 1/31 | 1/30 | 0/31 | 1/30 |
| Event | Ofatumumab 500 mg + Fludarabine and Cyclophosphamide (FC) | Ofatumumab 1000 mg + FC | Ofatumumab 500 mg + FC: Extended Follow-up Phase | Ofatumumab 1000 mg + FC: Extended Follow-up Phase |
|---|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 14/31 | 23/30 | — | — |
| LeukopeniaBlood and lymphatic system disorders | 8/31 | 16/30 | — | — |
| NauseaGastrointestinal disorders | 14/31 | 13/30 | — | — |
| ThrombocytopeniaBlood and lymphatic system disorders | 7/31 | 12/30 | — | — |
| RashSkin and subcutaneous tissue disorders | 10/31 | 8/30 | — | — |
| VomitingGastrointestinal disorders | 9/31 | 6/30 | — | — |
| PyrexiaGeneral disorders | 9/31 | 7/30 | — | — |
| FatigueGeneral disorders | 8/31 | 6/30 | — | — |
| CoughRespiratory, thoracic and mediastinal disorders | 4/31 | 7/30 | — | — |
| HeadacheNervous system disorders | 7/31 | 5/30 | — | — |
| Age, Continuous(Years) | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC | Total |
|---|---|---|---|
| Mean | 56.1 ± 8.4 | 56.4 ± 8.7 | 56.2 ± 8.5 |
| Sex: Female, Male(Participants) | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC | Total |
|---|---|---|---|
| Female | 11 | 7 | 18 |
| Male | 20 | 23 | 43 |
| Race/Ethnicity, Customized(participants) | Ofatumumab 500 mg + FC | Ofatumumab 1000 mg + FC | Total |
|---|---|---|---|
| White | 31 | 29 | 60 |
| Black or African American | 0 | 1 | 1 |
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