Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Given the tolerability and efficacy of ofatumumab in follicular lymphoma and Chronic Lymphocytic Leukemia, and the need to improve therapy for patients with WM utilizing a non-myelosuppressive agent this phase II trial of ofatumumab is being initiated in patients with Waldenstrom's Macroglobulinemia (WM).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ofatumumab | Experimental | Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ofatumumab | Biological | Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline. | Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment |
| Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline. | Baseline and up to Study Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Los Angeles | California | 90095-6984 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27914971 | Derived | Furman RR, Eradat HA, DiRienzo CG, Hofmeister CC, Hayman SR, Leonard JP, Coleman M, Advani R, Chanan-Khan A, Switzky J, Liao QM, Shah D, Jewell RC, Lisby S, Lin TS. Once-weekly ofatumumab in untreated or relapsed Waldenstrom's macroglobulinaemia: an open-label, single-arm, phase 2 study. Lancet Haematol. 2017 Jan;4(1):e24-e34. doi: 10.1016/S2352-3026(16)30166-1. Epub 2016 Dec 1. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5. |
| FG001 | 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline. | Intent-to-Treat (ITT) Population: all participants who were considered eligible for treatment and who had been exposed to study drug irrespective of the planned course of treatment. | Posted | Number | participants | Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment |
|
Participants were followed from baseline up to approximately 5 years.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 | Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Catheter site haemorrhage | General disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
Not provided
| ID | Term |
|---|---|
| D008258 | Waldenstrom Macroglobulinemia |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C527517 | ofatumumab |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment |
| Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline. | Baseline and up to Study Week 16 |
| Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | IgM is a basic antibody that is produced by B cells. It is the first antibody to appear in response to initial exposure to antigen. IgM flare is defined as an IgM level that increases by >25% from baseline (BL) and is associated with a response to treatment. Avoidance of IgM flare indicates the lack of an increase in IgM of >25% from BL. | Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment |
| Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator | Duration of response is defined as the time from the initial response to relapse/disease progression (DP) or death. DP for CR is defined as the reappearance of the IgM protein, new signs/symptoms attributable to WM, evidence of active disease or recurrence of bone marrow involvement by lymphoplasmacytic cells, or the appearance of any new lymph node >=1.5 centimeters on any axis. Progression for PR/MR is either a >=25% increase in IgM from the lowest attained response value or progression of lymphadenopathy, organomegaly, cytopenias, or other clinically significant signs/symptoms caused by WM. | From baseline up to approximately 5 years |
| Progression-free Survival | Time to disease progression is defined as the time from baseline to disease progression or death. | From baseline up to approximately 5 years |
| Time to Response for Responders | Time to response is defined as the time from baseline to the first response date. | From baseline up to approximately 5 years |
| Overall Survival | Overall survival is defined as the time from baseline until death due to any cause. | From baseline up to approximately 5 years |
| Clearance of Ofatumumab | Clearance (CL) is defined as the volume of plasma that is cleared of drug per unit of time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
| Volume of Distribution at Steady State of Ofatumumab | Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of the drug in the body at steady state. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
| Half-life of Ofatumumab | Half-life (t½) is defined as the time required for the concentration of the drug in plasma to decrease to one-half of its current value. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
| Cmax and Ctrough of Ofatumumab | Cmax is defined as the maximum observed drug concentration after administration, and Ctrough is defined as the drug concentration observed prior to the start of the next dose. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
| AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-tau) is the area under the drug concentration-time curve over the dosing interval (one week). AUC(0-inf) is the area under the drug concentration-time curve from time zero extrapolated to infinite time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
| Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result | All human-antihuman antibody (HAHA) samples were first tested in a screening assay to identify potential HAHA positives. Next, samples that tested positive in the screening assay were further tested in the confirmation assay to determine the specificity of the signal to ofatumumab. Confirmed positive samples were reported as positive. | From baseline up to approximately 5 years |
| Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | CD4+ and CD19+ are two key flow cytometry parameters, and total hemolytic complement (CD50) is a complement parameter. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline and Month 3 |
| Number of Participants With the Indicated SAEs Related to Study Drug | An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement. | From baseline up to approximately 5 years |
| Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study drug. | From baseline up to approximately 5 years |
| Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Certain AEs led to permanent discontinuation of study drug and hence resulted in their withdrawal from the study. | From baseline up to approximately 5 years |
| Number of Participants With the Indicated >=Grade 3 AEs | AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. | From baseline up to approximately 5 years |
| Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Infusion-related AEs are the AEs that resulted from administration of study drug through infusion. AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. | From baseline up to approximately 5 years |
| Stanford |
| California |
| 94305 |
| United States |
| GSK Investigational Site | Rochester | Minnesota | 55905 | United States |
| GSK Investigational Site | Buffalo | New York | 14263 | United States |
| GSK Investigational Site | New York | New York | 10021 | United States |
| GSK Investigational Site | Columbus | Ohio | 43210-1228 | United States |
| GSK Investigational Site | San Antonio | Texas | 78229 | United States |
| BG001 | 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| OG000 |
| 300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5 |
Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5. |
| OG001 | 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5. |
|
|
|
| Primary | Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline. | ITT Population | Posted | Number | participants | Baseline and up to Study Week 16 |
|
|
|
|
| Secondary | Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator | Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline. | ITT Population | Posted | Number | participants | Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment |
|
|
|
| Secondary | Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator | Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline. | ITT Population | Posted | Number | participants | Baseline and up to Study Week 16 |
|
|
|
| Secondary | Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) | IgM is a basic antibody that is produced by B cells. It is the first antibody to appear in response to initial exposure to antigen. IgM flare is defined as an IgM level that increases by >25% from baseline (BL) and is associated with a response to treatment. Avoidance of IgM flare indicates the lack of an increase in IgM of >25% from BL. | ITT Population. Only those participants who received Cycle 1 treatment (including the Redosing Cycle) were assessed. | Posted | Number | participants | Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment |
|
|
|
| Secondary | Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator | Duration of response is defined as the time from the initial response to relapse/disease progression (DP) or death. DP for CR is defined as the reappearance of the IgM protein, new signs/symptoms attributable to WM, evidence of active disease or recurrence of bone marrow involvement by lymphoplasmacytic cells, or the appearance of any new lymph node >=1.5 centimeters on any axis. Progression for PR/MR is either a >=25% increase in IgM from the lowest attained response value or progression of lymphadenopathy, organomegaly, cytopenias, or other clinically significant signs/symptoms caused by WM. | ITT Population. Only those participants classified as responders were included in the analysis. Participants who had disease progression or death were counted as events, and other participants were censored at the date of the last adequate assessment in the study. | Posted | Median | Inter-Quartile Range | days | From baseline up to approximately 5 years | events | events |
|
|
|
| Secondary | Progression-free Survival | Time to disease progression is defined as the time from baseline to disease progression or death. | ITT Population. Participants who experienced disease progression or death were counted as events, and other participants were censored at the time of the last adequate assessment in the study. | Posted | Median | Inter-Quartile Range | days | From baseline up to approximately 5 years | events | events |
|
|
|
| Secondary | Time to Response for Responders | Time to response is defined as the time from baseline to the first response date. | ITT Population. Only participants classified as responders (CR, PR, and MR) were assessed. | Posted | Median | 95% Confidence Interval | days | From baseline up to approximately 5 years |
|
|
|
| Secondary | Overall Survival | Overall survival is defined as the time from baseline until death due to any cause. | ITT Population. Only those participants who died during the study and during the follow-up period were assessed. | Posted | From baseline up to approximately 5 years |
|
|
| Secondary | Clearance of Ofatumumab | Clearance (CL) is defined as the volume of plasma that is cleared of drug per unit of time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | Pharmacokinetic (PK) Population: all participants from whom a PK sample was obtained and analyzed. Data were provided for the number of participants for whom the parameter could be determined. | Posted | Geometric Mean | 95% Confidence Interval | milliliters/hour (ml/hr) | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
|
|
|
| Secondary | Volume of Distribution at Steady State of Ofatumumab | Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of the drug in the body at steady state. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | PK Population. Data were provided for the number of participants for whom the parameter could be determined. | Posted | Geometric Mean | 95% Confidence Interval | Liters (L) | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
|
|
|
| Secondary | Half-life of Ofatumumab | Half-life (t½) is defined as the time required for the concentration of the drug in plasma to decrease to one-half of its current value. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | PK Population. Data were provided for the number of participants for whom the parameter could be determined. | Posted | Geometric Mean | 95% Confidence Interval | Days (d) | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
|
|
|
| Secondary | Cmax and Ctrough of Ofatumumab | Cmax is defined as the maximum observed drug concentration after administration, and Ctrough is defined as the drug concentration observed prior to the start of the next dose. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | PK Population. Data were provided for the number of participants attending each visit for whom the parameter could be determined. | Posted | Geometric Mean | 95% Confidence Interval | micrograms/milliliter (µg/ml) | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
|
|
|
| Secondary | AUC(0-tau) and AUC(0-inf) of Ofatumumab | AUC(0-tau) is the area under the drug concentration-time curve over the dosing interval (one week). AUC(0-inf) is the area under the drug concentration-time curve from time zero extrapolated to infinite time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle. | PK Population. Data were provided for the number of participants attending each visit for whom the parameter could be calculated.. | Posted | Geometric Mean | 95% Confidence Interval | micrograms X hours/milliliters (µg.h/mL) | From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7 |
|
|
|
| Secondary | Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result | All human-antihuman antibody (HAHA) samples were first tested in a screening assay to identify potential HAHA positives. Next, samples that tested positive in the screening assay were further tested in the confirmation assay to determine the specificity of the signal to ofatumumab. Confirmed positive samples were reported as positive. | Safety Population. Only those participants with post-ofatumumab HAHA results were analyzed. | Posted | Number | participants | From baseline up to approximately 5 years |
|
|
|
| Secondary | Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment | CD4+ and CD19+ are two key flow cytometry parameters, and total hemolytic complement (CD50) is a complement parameter. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | ITT Population: only participants with blood count data at both Baseline and Month 3 were included in the analysis. | Posted | Median | Full Range | cells per microliter (µL) | Baseline and Month 3 |
|
|
|
| Secondary | Number of Participants With the Indicated SAEs Related to Study Drug | An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement. | Safety Population. Only those participants who experienced an SAE categorized as being related to study drug were assessed. | Posted | Number | participants | From baseline up to approximately 5 years |
|
|
|
| Secondary | Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study drug. | Safety Population. Only those participants who experienced a study drug-related AE were assessed. | Posted | Number | participants | From baseline up to approximately 5 years |
|
|
|
| Secondary | Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study | Certain AEs led to permanent discontinuation of study drug and hence resulted in their withdrawal from the study. | Safety Population. Only those participants who experienced an AE leading to their withdrawal from the study were assessed. | Posted | Number | participants | From baseline up to approximately 5 years |
|
|
|
| Secondary | Number of Participants With the Indicated >=Grade 3 AEs | AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. | Safety Population. Only those participants who experienced a >=Grade 3 AE were assessed. | Posted | Number | participants | From baseline up to approximately 5 years |
|
|
|
| Secondary | Number of Participants With the Indicated Infusion-related >=Grade 3 AE | Infusion-related AEs are the AEs that resulted from administration of study drug through infusion. AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. | Safety Population. Only those participants who experienced >=Grade 3 infusion-related AEs were assessed. | Posted | Number | participants | From baseline up to approximately 5 years |
|
|
|
| 5 |
| 15 |
| 15 |
| 15 |
| EG001 | 300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5 | Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5. | 7 | 22 | 20 | 22 |
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Haemolysis | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Myocardial ischaemia | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Cryoglobulinaemia | Immune system disorders | MedDRA | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Fluid overload | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Haemorrhage subcutaneous | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Nail bed bleeding | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Chills | General disorders | MedDRA | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Oedema | General disorders | MedDRA | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
|
| Ill-defined disorder | General disorders | MedDRA | Systematic Assessment |
|
| Medical device pain | General disorders | MedDRA | Systematic Assessment |
|
| Pain | General disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Paraesthesia oral | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Lip swelling | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Polyneuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Restless legs syndrome | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Haemochromatosis | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Libido decreased | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA | Systematic Assessment |
|
| Pallor | Vascular disorders | MedDRA | Systematic Assessment |
|
| Raynaud's phenomenon | Vascular disorders | MedDRA | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Muscular pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Trismus | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Ear pruritus | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA | Systematic Assessment |
|
| Blood parathyroid hormone increased | Investigations | MedDRA | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA | Systematic Assessment |
|
| Serum sickness | Immune system disorders | MedDRA | Systematic Assessment |
|
| Von Willebrand's disease | Congenital, familial and genetic disorders | MedDRA | Systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Thirst | General disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Tongue ulceration | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
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.
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| percentage of participants |
| 64 |
| 2-Sided |
| 95 |
| 40.7 |
| 82.8 |
The estimated value represents the percentage of participants with OR. |
| Superiority or Other |
| MR |
|
| MR |
|
| >25% increase from BL, PR/MR response , n=7, 15 |
|
| =<25% increase from BL, PR/MR response , n=7, 15 |
|
| Cmax, Course 1 Dose 4, n=13,0 |
|
| Cmax, Course 1 Dose 5, n=0,18 |
|
| Ctrough, Course 1 Dose 2, n=7,12 |
|
| Ctrough, Course 1 Dose 3, n=11,19 |
|
| Ctrough, Course 1 Dose 4, n=13,21 |
|
| Ctrough, Course 1 Dose 5, n=0,18 |
|
| Cmax, Course 2 Dose 1, n=9,11 |
|
| Cmax, Course 2 Dose 3, n=8,12 |
|
| Cmax, Course 2 Dose 5, n=10,12 |
|
| Ctrough, Course 2 Dose 2, n=7,10 |
|
| Ctrough, Course 2 Dose 3, n=8,12 |
|
| Ctrough, Course 2 Dose 4, n=11,12 |
|
| Ctrough, Course 2 Dose 5, n=11,12 |
|
| AUC(0-inf), Course 1 Dose 4, n=9,0 |
|
| AUC(0-inf), Course 1 Dose 5, n=0,18 |
|
| AUC(0-tau), Course 2 Dose 5, n=10,12 |
|
| AUC(0-inf), Course 2 Dose 5, n=8,12 |
|
| CD50 |
|
| Cryoglobulinaemia |
|
| Fluid overload |
|
| Renal failure acute |
|
| Pulmonary oedema |
|
| Rash |
|
| Pruritus generalised |
|
| Hyperhidrosis |
|
| Erythema |
|
| Palmar erythema |
|
| Rash macular |
|
| Swelling face |
|
| Throat irritation |
|
| Nasal congestion |
|
| Oropharyngeal pain |
|
| Dyspnoea |
|
| Epistaxis |
|
| Painful respiration |
|
| Pulmonary oedema |
|
| Rhinitis allergic |
|
| Rhinorrhoea |
|
| Sneezing |
|
| Pyrexia |
|
| Chills |
|
| Chest pain |
|
| Chest discomfort |
|
| Fatigue |
|
| Non-cardiac chest pain |
|
| Asthenia |
|
| Ill-defined disorder |
|
| Local swelling |
|
| Malaise |
|
| Pain |
|
| Abdominal pain |
|
| Diarrhoea |
|
| Nausea |
|
| Paraesthesia oral |
|
| Abdominal discomfort |
|
| Dyspepsia |
|
| Hypoaesthesia oral |
|
| Lip swelling |
|
| Oral pain |
|
| Oral pruritus |
|
| Stomatitis |
|
| Flushing |
|
| Hypotension |
|
| Back pain |
|
| Limb discomfort |
|
| Muscle spasms |
|
| Musculoskeletal pain |
|
| Myalgia |
|
| Trismus |
|
| Anaemia |
|
| Haemolysis |
|
| Leukopenia |
|
| Lymph node pain |
|
| Neutropenia |
|
| Ear pruritus |
|
| Eye pruritus |
|
| Ocular hyperaemia |
|
| Abnormal sensation in eye |
|
| Eye swelling |
|
| Decreased appetite |
|
| Fluid overload |
|
| Hypophagia |
|
| Increased appetite |
|
| Headache |
|
| Paraesthesia |
|
| Sinus headache |
|
| Infusion related reaction |
|
| Blood creatinine increased |
|
| Body temperature increased |
|
| Protein total increased |
|
| Hypersensitivity |
|
| Serum sickness |
|
| Rhinitis |
|
| Urinary tract infection |
|
| Bradycardia |
|
| Insomnia |
|
| Renal failure acute |
|
| Thirst |
|
| Vomiting |
|
| Cryoglobulinaemia |
|
| Pallor |
|
| Arthralgia |
|
| Fluid retention |
|
| Hypoaesthesia |
|
| Psychomotor hyperactivity |
|
| Weight decreased |
|
| Myocardial ischaemia |
|
| Fluid overload |
|
| Renal failure acute |
|
| Pulmonary oedema |
|
| Haemolytic anaemia |
|
| Febrile neutropenia |
|
| Haemolytic anaemia |
|
| Chest pain |
|
| Chest discomfort |
|
| Pyrexia |
|
| Blood creatinine increased |
|
| Haemoglobin decreased |
|
| Protein total increased |
|
| Dyspnoea exertional |
|
| Epistaxis |
|
| Pulmonary oedema |
|
| Cryoglobulinaemia |
|
| Serum sickness |
|
| Dizziness |
|
| Headache |
|
| Syncope |
|
| Myocardial ischaemia |
|
| Abdominal discomfort |
|
| Urinary tract infection |
|
| Fluid overload |
|
| Back pain |
|
| Renal failure acute |
|
| Rash |
|
| Neutropenia |
|
| Fatigue |
|
| Small intestinal obstruction |
|
| Back pain |
|
| Rash |
|