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| ID | Type | Description | Link |
|---|---|---|---|
| OMB110911 | Other Identifier | Novartis |
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Majority of patients (62%) had been treated with next line therapies, including new highly effective therapies confounding the interpretation of the OS results.
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The purpose of this study was to evaluate the safety and efficacy of ofatumumab added to chlorambucil in patients with untreated Chronic Lymphocytic Leukemia.
Chlorambucil, is currently approved for treatment of frontline chronic lymphocytic leukemia, especially, but not limited to the ailing and elderly patient population. Several other more aggressive treatment options are available (e.g. fludarabine), however they are not suitable for all CLL patients, especially the ailing and elderly, due to greater toxicity. Ofatumumab is effective with low toxicity. The addition of ofatumumab to chlorambucil offers potentially a more effective therapy, with limited toxicity. The objective of this study was to evaluate progression-free survival (PFS), overall response and overall survival in subjects with previously untreated CLL with ofatumumab added to chlorambucil versus chlorambucil.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ofatumumab + chlorambucil | Experimental | ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles |
|
| chlorambucil | Active Comparator | chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| chlorambucil, tablets | Drug | 2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles |
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| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS), as Assessed by the Independent Review Committee (IRC) | PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (PD) and the date of death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event or death occurred after extensive lost-to-follow-up time or if new anti-cancer therapy was started were censored at the date of the last visit with adequate assessment. | From randomization to the date of first documented disease progression or death due to any cause, whichever occured first, reported between day of first patient randomized up to about 49 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With the Best Overall Response (OR), as Assessed by the IRC | OR is defined as the number of participants achieving an objective response (complete response [CR], CR with incomplete bone marrow recovery [CRi], partial response [PR], and nodular PR [nPR]). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Sedona | Arizona | 86336 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33054084 | Derived | Tausch E, Beck P, Schlenk RF, Jebaraj BJ, Dolnik A, Yosifov DY, Hillmen P, Offner F, Janssens A, Babu GK, Grosicki S, Mayer J, Panagiotidis P, McKeown A, Gupta IV, Skorupa A, Pallaud C, Bullinger L, Mertens D, Dohner H, Stilgenbauer S. Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. Haematologica. 2020 Oct 1;105(10):2440-2447. doi: 10.3324/haematol.2019.229161. | |
| 25882396 |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Eligible participants (par.) were stratified by age (<65 years vs. >=65years), stage (Binet A vs. B vs. C) and Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2). Participants in each stratum were then centrally randomized in a 1:1 ratio to receive ofatumumab plus chlorambucil (O+CHL) or chlorambucil alone (CHL).
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| ID | Title | Description |
|---|---|---|
| FG000 | Chlorambucil | Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
| FG001 | Ofatumumab + Chlorambucil |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| ofatumumab (GSK1841157) infusion | Drug | iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; |
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| From randomization until the 259th PFS event occurred, up to about 49 months |
| Number of Participants Who Were Negative for Minimal Residual Disease (MRD) | MRD was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes. | From randomization until the 259th PFS event occurred (Median follow-up approximately 28.9 months) |
| Overall Survival | Overall survival is defined as the time from randomization to death due to any cause. Each participant was followed at the time when the total IRC-assessed PFS events occurred. Participants who had not died were censored at the date of last contact. | From randomization up to about 111 months |
| Time to Response, as Assessed by the IRC | Time to response is defined as the time from randomization to the first response (CR, CRi, nPR, or PR). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. Participants with unknown or missing responses were considered as non-responders. Only responders (CR, CRi, PR, nPR) were included in the analysis. | From randomization uo to about 27 months |
| Duration of Response (DOR), as Assessed by the IRC | DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time (>= 12 weeks) were censored at the date of the last visit with adequate assessment. Par. with unknown or missing responses were considered as non-responders. | From randomization up to about 43 months |
| Time to Progression, as Assessed by the IRC | Time to progression is defined as the time from the date of randomization to disease progression (PD). PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Participants who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time were censored at the date of the last visit with adequate assessment. | From randomization up to about 49 months |
| Time to Next Therapy | Time to next therapy is defined as the time from randomization until the start of the next-line of treatment. | From randomization up to about 49 months |
| Number of Participants With Improvement in ECOG Performance Status of 0 or 1 | The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, how the disease affects the daily living, and determines appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead. Participants with an ECOG performance status of 0 or 1 are shown.. | Baseline, Cycle 3 Day 1, 1 month Follow-up |
| Number of Participants With Improvement in Constitutional Symptoms (CS) | Assessment for the presence of the following symptoms were performed at Screening, Day 1 of each treatment cycle and at every Follow-up visit: night sweats (without signs of infection); unexplained, unintentional weight loss >= 10% within the previous 6 months; recurrent, unexplained fever of greater than 38 degrees celsius or 100.5 degrees fahrenheit for 2 weeks; and extreme fatigue. The best response refers to overall best response in terms of CR, CRi, PR or nPR. Data are presented for constitutional response= yes and no. | Baseline, Cycle 3 Day 1, and 1 month Follow-up |
| Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result | Serum samples for analysis of HAHA were collected at Baseline (Screening), Cycle 4 Day 1 (after 3 months of treatment), and at 1 month and 6 months post last dose of ofatumumab. All samples were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA-positive and further evaluated in the titration test to obtain a titer of HAHA. | Baseline, Cycle 4 Day 1, 1 Month Follow-up, and 6 Month Follow-up |
| Cmax and Ctrough of Ofatumumab | Blood samples were collected to assess the plasma concentration of ofatumumab. Maximum concentration (Cmax) and observed drug concentration prior to the next dose (Ctrough) were determined. Blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of treatment. | Cycle 1 Day 1,Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, and Cycle 9 Day 1 |
| Total Plasma Clearance (CL) of Ofatumumab | Plasma clearance is defined as the plasma volume which is totally cleared of drug per unit of time. Blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to the ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on duration of treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment. | Cycle 4 Day 1 |
| AUC(0-tau) of Ofatumumab | Area under the concentration time curve over the dosing interval [AUC(0-tau)] is a measure of drug exposure over time. AUC(0-tau) is defined as the area under the ofatumumab plasma concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of ofatumumab. For estimation of AUC(0-tau), blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hous after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to the ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on duration of treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment. | Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1 |
| Volume of Distribution at Steady State (Vss) of Ofatumumab | Volume of distribution at steady state (Vss) is defined as the distribution of a drug between plasma and the rest of the body at steady state. Blood samples were collected from participants who received ofatumumab plus chlorambucil at predose and 0.5 hour after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of the treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment. | Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1 |
| Plasma Half Life (t1/2) of Ofatumumab | The terminal half-life (t1/2) of ofatumumab is defined as the time required for the plasma concentration of ofatumumab to reach half of its original concentration. Blood samples were collected to assess the plasma half-life of ofatumumab. Blood samples were collected from participants who received ofatumumab plus chlorambucil pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of the treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment. | Cycle 4 Day 1 |
| Dose-normalized Cmax of Chlorambucil and Phenylacetic Acid Mustard (PAAM) | Blood samples for the determination of serum concentrations of chlorambucil and its metabolite PAAM were collected from participants in a substudy on Cycle 3 Day 1. The maximum observed concentration (Cmax) of chlorambucil and PAAM normalized to the administered dose was determined as a measure of exposure and compared to reference data from a prior study (LEUA1001) [No NCT number available for this study; GlaxoSmithKline Document Number RM1998/00449/00]. | Cycle 3 Day 1 |
| Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM) | Blood samples for the determination of serum concentrations of chlorambucil and its metabolite PAAM were collected from participants in a substudy on Cycle 3 Day 1. The area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) and over 6 hours (AUC[0-6]) of chlorambucil and AUC(0-6) of PAAM normalized to the administered dose was determined as a measure of exposure and compared to reference data from a prior study (LEUA1001) [No NCT number available for this study; GlaxoSmithKline Document Number RM1998/00449/00]. | Cycle 3 Day 1 |
| Change From Baseline in Health Related Quality of Life (HRQOL) | HRQOL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTCQLQC30), Chronic Lymphocytic Leukemia module (EORTC QLQ-CLL16), EuorQoL-Five Dimension (EQ-5D), and HCQ. Period (P)1 (Day 85, Day 169, Day 253) and P2 (scheduled follow-up (FU) and withdrawal visits) analysis were considered. Baseline (BL) for P1 was defined as score from screening visit and BL for P2 was defined as the last on-treatment score. The 2 principal QoL outcomes were pre-specified as the Global Health scale (GHS/QOL) of the EORTC QLQ-C30 and fatigue scale of the EORTC QLQ-CLL16. For EORTC QLQ-C30,GHS/Qol, the possible scale range was 0-100 (with 100 being 'best') and a positive difference from BL is indicative of better functioning (range -100 to +100). For the EORTC QLQ-CLL16 fatigue scale, the possible scale range was 0-100 (with 0 being 'best') and a negative difference from BL represents an improvement in fatigue (range -100 to +100). | Baseline, Cycle 4 day 1, cycle 7 day 1, 1 month follow-up, 6 month follow-up, 12 month follow-up |
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. | From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months. |
| Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. Maximum severity grades were evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death). | From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months. |
| Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia) | Participants with a Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented by treatment cycle. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death). | From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months. |
| Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) Disease | AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented. | From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months. |
| Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study | Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products are counted in this table. | From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 28.9 months) |
| Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM | Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | From start of treatment up to 30 days after last treatment |
| Tucson |
| Arizona |
| 85704 |
| United States |
| Novartis Investigative Site | Murrieta | California | 92562 | United States |
| Novartis Investigative Site | Aurora | Colorado | 80012 | United States |
| Novartis Investigative Site | Denver | Colorado | 80204 | United States |
| Novartis Investigative Site | Boca Raton | Florida | 33486 | United States |
| Novartis Investigative Site | New Port Richey | Florida | 34655 | United States |
| Novartis Investigative Site | Ocala | Florida | 34471 | United States |
| Novartis Investigative Site | Ocoee | Florida | 34761 | United States |
| Novartis Investigative Site | Marietta | Georgia | 30060 | United States |
| Novartis Investigative Site | Chicago | Illinois | 60612 | United States |
| Novartis Investigative Site | Indianapolis | Indiana | 46227 | United States |
| Novartis Investigative Site | Lee's Summit | Missouri | 64064 | United States |
| Novartis Investigative Site | Raleigh | North Carolina | 27607 | United States |
| Novartis Investigative Site | Abilene | Texas | 79606-5208 | United States |
| Novartis Investigative Site | Arlington | Texas | 76014 | United States |
| Novartis Investigative Site | Austin | Texas | 78731 | United States |
| Novartis Investigative Site | Dallas | Texas | 75230 | United States |
| Novartis Investigative Site | Dallas | Texas | 75231 | United States |
| Novartis Investigative Site | Fort Worth | Texas | 76104 | United States |
| Novartis Investigative Site | Midland | Texas | 79701 | United States |
| Novartis Investigative Site | Odessa | Texas | 79761 | United States |
| Novartis Investigative Site | San Antonio | Texas | 78217 | United States |
| Novartis Investigative Site | San Antonio | Texas | 78229 | United States |
| Novartis Investigative Site | Tyler | Texas | 75702 | United States |
| Novartis Investigative Site | Waco | Texas | 76712 | United States |
| Novartis Investigative Site | Webster | Texas | 77598-4420 | United States |
| Novartis Investigative Site | Seattle | Washington | 98133 | United States |
| Novartis Investigative Site | Vancouver | Washington | 98684 | United States |
| Novartis Investigative Site | Yakima | Washington | 98902 | United States |
| Novartis Investigative Site | Bruges | 8000 | Belgium |
| Novartis Investigative Site | Brussels | 1200 | Belgium |
| Novartis Investigative Site | Ghent | 9000 | Belgium |
| Novartis Investigative Site | Haine-Saint-Paul | 7100 | Belgium |
| Novartis Investigative Site | Leuven | 3000 | Belgium |
| Novartis Investigative Site | Porto Alegre | Rio de Janeiro | 91350-200 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 05403-000 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 05651-901 | Brazil |
| Novartis Investigative Site | Toronto | Ontario | M4N 3M5 | Canada |
| Novartis Investigative Site | Montreal | Quebec | H3A1A1 | Canada |
| Novartis Investigative Site | Sherbrooke | Quebec | J1H 5N4 | Canada |
| Novartis Investigative Site | Brno | 625 00 | Czechia |
| Novartis Investigative Site | Hradec Králové | Czechia |
| Novartis Investigative Site | Prague | 100 34 | Czechia |
| Novartis Investigative Site | Créteil | 94010 | France |
| Novartis Investigative Site | Pierre-Bénite | 69495 | France |
| Novartis Investigative Site | Karlsruhe | Baden-Wurttemberg | 76137 | Germany |
| Novartis Investigative Site | Mannheim | Baden-Wurttemberg | 68161 | Germany |
| Novartis Investigative Site | Stuttgart | Baden-Wurttemberg | 70190 | Germany |
| Novartis Investigative Site | Ulm | Baden-Wurttemberg | 89081 | Germany |
| Novartis Investigative Site | Erlangen | Bavaria | 91052 | Germany |
| Novartis Investigative Site | Munich | Bavaria | 81241 | Germany |
| Novartis Investigative Site | Regensburg | Bavaria | 93049 | Germany |
| Novartis Investigative Site | Würzburg | Bavaria | 97070 | Germany |
| Novartis Investigative Site | Frankfurt am Main | Hesse | 65929 | Germany |
| Novartis Investigative Site | Kassel | Hesse | 34119 | Germany |
| Novartis Investigative Site | Hanover | Lower Saxony | 30625 | Germany |
| Novartis Investigative Site | Lehrte | Lower Saxony | 31275 | Germany |
| Novartis Investigative Site | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Novartis Investigative Site | Essen | North Rhine-Westphalia | 45122 | Germany |
| Novartis Investigative Site | Moenchengladbach-Rheydt | North Rhine-Westphalia | 41239 | Germany |
| Novartis Investigative Site | Münster | North Rhine-Westphalia | 48149 | Germany |
| Novartis Investigative Site | Saarbrücken | Saarland | 66113 | Germany |
| Novartis Investigative Site | Athens | 11 527 | Greece |
| Novartis Investigative Site | Thessaloniki | 564 29 | Greece |
| Novartis Investigative Site | Thessaloniki | 57010 | Greece |
| Novartis Investigative Site | Ahmedabad | 380009 | India |
| Novartis Investigative Site | Bangalore | 560029 | India |
| Novartis Investigative Site | Mumbai | 400012 | India |
| Novartis Investigative Site | Mumbai | 400014 | India |
| Novartis Investigative Site | New Delhi | 110029 | India |
| Novartis Investigative Site | Pune | 411001 | India |
| Novartis Investigative Site | Cork | Ireland |
| Novartis Investigative Site | Dublin | 7 | Ireland |
| Novartis Investigative Site | Galway | Ireland |
| Novartis Investigative Site | James Street | 8 | Ireland |
| Novartis Investigative Site | Limerick | Ireland |
| Novartis Investigative Site | Tullamore | Ireland |
| Novartis Investigative Site | Waterford | Ireland |
| Novartis Investigative Site | Bari | Apulia | 70124 | Italy |
| Novartis Investigative Site | Potenza | Basilicate | 85100 | Italy |
| Novartis Investigative Site | Naples | Campania | 80131 | Italy |
| Novartis Investigative Site | Albano Laziale (Roma) | Lazio | 00041 | Italy |
| Novartis Investigative Site | Genoa | Liguria | 16132 | Italy |
| Novartis Investigative Site | Brescia | Lombardy | 25123 | Italy |
| Novartis Investigative Site | Milan | Lombardy | 20132 | Italy |
| Novartis Investigative Site | Milan | Lombardy | 20133 | Italy |
| Novartis Investigative Site | Milan | Lombardy | 20162 | Italy |
| Novartis Investigative Site | Novara | Piedmont | 28100 | Italy |
| Novartis Investigative Site | Palermo | Sicily | 90146 | Italy |
| Novartis Investigative Site | Ascoli Piceno | The Marches | 63100 | Italy |
| Novartis Investigative Site | Venezia - Mestre | Veneto | 30174 | Italy |
| Novartis Investigative Site | Vicenza | Veneto | 36100 | Italy |
| Novartis Investigative Site | Udine | 33100 | Italy |
| Novartis Investigative Site | Amersfoort | 3818 ES | Netherlands |
| Novartis Investigative Site | Amsterdam | 1105 AZ | Netherlands |
| Novartis Investigative Site | Groningen | 9713 GZ | Netherlands |
| Novartis Investigative Site | Nijmegen | 6525 GA | Netherlands |
| Novartis Investigative Site | Rotterdam | 3015 CE | Netherlands |
| Novartis Investigative Site | Rotterdam | 3075 EA | Netherlands |
| Novartis Investigative Site | The Hague | 2545 CH | Netherlands |
| Novartis Investigative Site | Bialystok | 15-276 | Poland |
| Novartis Investigative Site | Chorzów | 41-500 | Poland |
| Novartis Investigative Site | Lodz | 93-510 | Poland |
| Novartis Investigative Site | Słupsk | 76-200 | Poland |
| Novartis Investigative Site | Warsaw | 02-776 | Poland |
| Novartis Investigative Site | Wroclaw | 50-367 | Poland |
| Novartis Investigative Site | Moscow | 115478 | Russia |
| Novartis Investigative Site | Moscow | 125101 | Russia |
| Novartis Investigative Site | Moscow | 125167 | Russia |
| Novartis Investigative Site | Novosibirsk | 630051 | Russia |
| Novartis Investigative Site | Saint Petersburg | 197 089 | Russia |
| Novartis Investigative Site | St'Petersburg | 191024 | Russia |
| Novartis Investigative Site | Barcelona | 08003 | Spain |
| Novartis Investigative Site | Barcelona | 08025 | Spain |
| Novartis Investigative Site | Hospitalet de Llobregat (Barcelona) | 08907 | Spain |
| Novartis Investigative Site | Madrid | 28006 | Spain |
| Novartis Investigative Site | Madrid | 28041 | Spain |
| Novartis Investigative Site | Madrid | 28046 | Spain |
| Novartis Investigative Site | Salamanca | 37007 | Spain |
| Novartis Investigative Site | Valencia | 46010 | Spain |
| Novartis Investigative Site | Luleå | SE-971 80 | Sweden |
| Novartis Investigative Site | Stockholm | SE-141 86 | Sweden |
| Novartis Investigative Site | Uppsala | SE-751 85 | Sweden |
| Novartis Investigative Site | Plymouth | Devon | PL6 8DH | United Kingdom |
| Novartis Investigative Site | Taunton | Somerset | TA1 5DA | United Kingdom |
| Novartis Investigative Site | Sunderland | Tyne | SR4 7TP | United Kingdom |
| Novartis Investigative Site | Bath | BA1 3NG | United Kingdom |
| Novartis Investigative Site | Belfast | BT9 7AB | United Kingdom |
| Novartis Investigative Site | Birmingham | B9 5SS | United Kingdom |
| Novartis Investigative Site | Bournemouth | BH7 7DW | United Kingdom |
| Novartis Investigative Site | Bradford | BD9 6RJ | United Kingdom |
| Novartis Investigative Site | Cambridge | CB2 0QQ | United Kingdom |
| Novartis Investigative Site | Canterbury, Kent | United Kingdom |
| Novartis Investigative Site | Carshalton | SM5 1AA | United Kingdom |
| Novartis Investigative Site | Cornwall | TR1 3LJ | United Kingdom |
| Novartis Investigative Site | Dudley | DY1 2HQ | United Kingdom |
| Novartis Investigative Site | Exeter | EX2 5DW | United Kingdom |
| Novartis Investigative Site | Glasgow | G12 OYN | United Kingdom |
| Novartis Investigative Site | Leeds | LS9 7TF | United Kingdom |
| Novartis Investigative Site | Liverpool | L7 8XP | United Kingdom |
| Novartis Investigative Site | London | EC1M 6BQ | United Kingdom |
| Novartis Investigative Site | London | SE5 9RS | United Kingdom |
| Novartis Investigative Site | Manchester | M13 9WL | United Kingdom |
| Novartis Investigative Site | Milton Keynes | MK6 5LD | United Kingdom |
| Novartis Investigative Site | Newcastle upon Tyne | NE7 7DN | United Kingdom |
| Novartis Investigative Site | Norwich | NR4 7UY | United Kingdom |
| Novartis Investigative Site | Oxford | OX3 7LJ | United Kingdom |
| Novartis Investigative Site | Peterborough | PE3 9GZ | United Kingdom |
| Novartis Investigative Site | Rhyl, Denbighshire | LL18 5UJ | United Kingdom |
| Novartis Investigative Site | Salford | M6 8HD | United Kingdom |
| Novartis Investigative Site | Stoke-on-Trent | ST4 6QG | United Kingdom |
| Novartis Investigative Site | Swindon | SN3 6BB | United Kingdom |
| Novartis Investigative Site | Uxbridge | UB8 3NN | United Kingdom |
| Derived |
| Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, Pettitt AR, Boyd T, Montillo M, Gupta IV, Wright O, Dixon I, Carey JL, Chang CN, Lisby S, McKeown A, Offner F; COMPLEMENT 1 Study Investigators. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015 May 9;385(9980):1873-83. doi: 10.1016/S0140-6736(15)60027-7. Epub 2015 Apr 14. |
| 25103870 | Derived | Jewell RC, Laubscher K, Lewis E, Fang L, Gafoor Z, Carey J, McKeown A, West S, Wright O, Sedoti D, Dixon I, Hottenstein CS, Chan G. Assessment of the effect of ofatumumab on cardiac repolarization. J Clin Pharmacol. 2015 Jan;55(1):114-21. doi: 10.1002/jcph.376. Epub 2014 Aug 21. |
Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
| COMPLETED |
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| NOT COMPLETED |
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Intent-to-treat (ITT) population: All randomized subjects regardless of whether or not they received study treatment.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Chlorambucil | Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
| BG001 | Ofatumumab + Chlorambucil | Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
| BG002 | Total | Total of all reporting groups |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Customized | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Progression-Free Survival (PFS), as Assessed by the Independent Review Committee (IRC) | PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (PD) and the date of death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event or death occurred after extensive lost-to-follow-up time or if new anti-cancer therapy was started were censored at the date of the last visit with adequate assessment. | Intent-to-Treat (ITT) Population: all par. randomized to study treatment regardless of whether or not they received treatment. PFS was assessed by a blinded independent review committee according to the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines. | Posted | Median | 95% Confidence Interval | Months | From randomization to the date of first documented disease progression or death due to any cause, whichever occured first, reported between day of first patient randomized up to about 49 months |
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| Secondary | Number of Participants With the Best Overall Response (OR), as Assessed by the IRC | OR is defined as the number of participants achieving an objective response (complete response [CR], CR with incomplete bone marrow recovery [CRi], partial response [PR], and nodular PR [nPR]). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. | ITT population. Only those participants with data available at the indicated time points were analyzed. OR was according to the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines. The 95% exact binomial confidence interval is for CR+CRi+nPR+PR. | Posted | Number | Participants | From randomization until the 259th PFS event occurred, up to about 49 months |
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| Secondary | Number of Participants Who Were Negative for Minimal Residual Disease (MRD) | MRD was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes. | ITT population. Only those participants with data available at the indicated time points were analyzed. | Posted | Number | Participants | From randomization until the 259th PFS event occurred (Median follow-up approximately 28.9 months) |
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| Secondary | Overall Survival | Overall survival is defined as the time from randomization to death due to any cause. Each participant was followed at the time when the total IRC-assessed PFS events occurred. Participants who had not died were censored at the date of last contact. | ITT population. Only those participants with data available at the indicated time points were analyzed. | Posted | Median | 95% Confidence Interval | Months | From randomization up to about 111 months |
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| Secondary | Time to Response, as Assessed by the IRC | Time to response is defined as the time from randomization to the first response (CR, CRi, nPR, or PR). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. Participants with unknown or missing responses were considered as non-responders. Only responders (CR, CRi, PR, nPR) were included in the analysis. | ITT population. Time to response was measured using the International Workshop for CLL (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines 2008. | Posted | Median | 95% Confidence Interval | Months | From randomization uo to about 27 months |
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| Secondary | Duration of Response (DOR), as Assessed by the IRC | DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time (>= 12 weeks) were censored at the date of the last visit with adequate assessment. Par. with unknown or missing responses were considered as non-responders. | ITT population. Only those participants with data available at the indicated time points were analyzed. Only responders (CR, CRi, PR, nPR) were included in the analysis. | Posted | Median | 95% Confidence Interval | Months | From randomization up to about 43 months |
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| Secondary | Time to Progression, as Assessed by the IRC | Time to progression is defined as the time from the date of randomization to disease progression (PD). PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Participants who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time were censored at the date of the last visit with adequate assessment. | ITT population. Only those participants with data available at the indicated time points were analyzed. | Posted | Median | 95% Confidence Interval | Months | From randomization up to about 49 months |
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| Secondary | Time to Next Therapy | Time to next therapy is defined as the time from randomization until the start of the next-line of treatment. | ITT population. Only those participants with data available at the indicated time points were analyzed. | Posted | Median | 95% Confidence Interval | Months | From randomization up to about 49 months |
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| Secondary | Number of Participants With Improvement in ECOG Performance Status of 0 or 1 | The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, how the disease affects the daily living, and determines appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead. Participants with an ECOG performance status of 0 or 1 are shown.. | ITT population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population. | Posted | Number | Participants | Baseline, Cycle 3 Day 1, 1 month Follow-up |
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| Secondary | Number of Participants With Improvement in Constitutional Symptoms (CS) | Assessment for the presence of the following symptoms were performed at Screening, Day 1 of each treatment cycle and at every Follow-up visit: night sweats (without signs of infection); unexplained, unintentional weight loss >= 10% within the previous 6 months; recurrent, unexplained fever of greater than 38 degrees celsius or 100.5 degrees fahrenheit for 2 weeks; and extreme fatigue. The best response refers to overall best response in terms of CR, CRi, PR or nPR. Data are presented for constitutional response= yes and no. | ITT population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population. | Posted | Number | Participants | Baseline, Cycle 3 Day 1, and 1 month Follow-up |
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| Secondary | Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result | Serum samples for analysis of HAHA were collected at Baseline (Screening), Cycle 4 Day 1 (after 3 months of treatment), and at 1 month and 6 months post last dose of ofatumumab. All samples were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA-positive and further evaluated in the titration test to obtain a titer of HAHA. | Safety population: all participants who received at least 1 dose of a study drug. Only participants with post-ofatumumab HAHA Results are included. | Posted | Number | Participants | Baseline, Cycle 4 Day 1, 1 Month Follow-up, and 6 Month Follow-up |
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| Secondary | Cmax and Ctrough of Ofatumumab | Blood samples were collected to assess the plasma concentration of ofatumumab. Maximum concentration (Cmax) and observed drug concentration prior to the next dose (Ctrough) were determined. Blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of treatment. | Pharmacokinetic (PK) Population: all participants for whom a pharmacokinetic sample was obtained and analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms/Milliliter (µg/mL) | Cycle 1 Day 1,Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, and Cycle 9 Day 1 |
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| Secondary | Total Plasma Clearance (CL) of Ofatumumab | Plasma clearance is defined as the plasma volume which is totally cleared of drug per unit of time. Blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to the ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on duration of treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Milliliter/hour (mL/h) | Cycle 4 Day 1 |
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| Secondary | AUC(0-tau) of Ofatumumab | Area under the concentration time curve over the dosing interval [AUC(0-tau)] is a measure of drug exposure over time. AUC(0-tau) is defined as the area under the ofatumumab plasma concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of ofatumumab. For estimation of AUC(0-tau), blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hous after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to the ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on duration of treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment. | PK Population. Only those participants available at the indicated time points were assessed. The number of participants assessed at each time point is indicated by "n=X,X. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg x hours/mL | Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1 |
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| Secondary | Volume of Distribution at Steady State (Vss) of Ofatumumab | Volume of distribution at steady state (Vss) is defined as the distribution of a drug between plasma and the rest of the body at steady state. Blood samples were collected from participants who received ofatumumab plus chlorambucil at predose and 0.5 hour after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of the treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment. | PK Population. Only those participants available at the indicated time points were assessed. The number of participants assessed at each time point is indicated by "n=X,X. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1 |
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| Secondary | Plasma Half Life (t1/2) of Ofatumumab | The terminal half-life (t1/2) of ofatumumab is defined as the time required for the plasma concentration of ofatumumab to reach half of its original concentration. Blood samples were collected to assess the plasma half-life of ofatumumab. Blood samples were collected from participants who received ofatumumab plus chlorambucil pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of the treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Cycle 4 Day 1 |
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| Secondary | Dose-normalized Cmax of Chlorambucil and Phenylacetic Acid Mustard (PAAM) | Blood samples for the determination of serum concentrations of chlorambucil and its metabolite PAAM were collected from participants in a substudy on Cycle 3 Day 1. The maximum observed concentration (Cmax) of chlorambucil and PAAM normalized to the administered dose was determined as a measure of exposure and compared to reference data from a prior study (LEUA1001) [No NCT number available for this study; GlaxoSmithKline Document Number RM1998/00449/00]. | Chlorambucil/PAAM pharmacokinetic (PK) Population (substudy): all participants for whom a chlorambucil/PAAM sample is obtained and analyzed. | Posted | Geometric Mean | Standard Deviation | nanograms per milliliter per milligram | Cycle 3 Day 1 |
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| Secondary | Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM) | Blood samples for the determination of serum concentrations of chlorambucil and its metabolite PAAM were collected from participants in a substudy on Cycle 3 Day 1. The area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) and over 6 hours (AUC[0-6]) of chlorambucil and AUC(0-6) of PAAM normalized to the administered dose was determined as a measure of exposure and compared to reference data from a prior study (LEUA1001) [No NCT number available for this study; GlaxoSmithKline Document Number RM1998/00449/00]. | Chlorambucil/PAAM pharmacokinetic (PK) Population (substudy): all participants for whom a chlorambucil/PAAM sample is obtained and analyzed. | Posted | Geometric Mean | Standard Deviation | Hours*nanogram/milliliter/milligram | Cycle 3 Day 1 |
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| Secondary | Change From Baseline in Health Related Quality of Life (HRQOL) | HRQOL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTCQLQC30), Chronic Lymphocytic Leukemia module (EORTC QLQ-CLL16), EuorQoL-Five Dimension (EQ-5D), and HCQ. Period (P)1 (Day 85, Day 169, Day 253) and P2 (scheduled follow-up (FU) and withdrawal visits) analysis were considered. Baseline (BL) for P1 was defined as score from screening visit and BL for P2 was defined as the last on-treatment score. The 2 principal QoL outcomes were pre-specified as the Global Health scale (GHS/QOL) of the EORTC QLQ-C30 and fatigue scale of the EORTC QLQ-CLL16. For EORTC QLQ-C30,GHS/Qol, the possible scale range was 0-100 (with 100 being 'best') and a positive difference from BL is indicative of better functioning (range -100 to +100). For the EORTC QLQ-CLL16 fatigue scale, the possible scale range was 0-100 (with 0 being 'best') and a negative difference from BL represents an improvement in fatigue (range -100 to +100). | ITT population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline, Cycle 4 day 1, cycle 7 day 1, 1 month follow-up, 6 month follow-up, 12 month follow-up |
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| Secondary | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. | Safety Population | Posted | Number | Participants | From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months. |
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| Secondary | Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. Maximum severity grades were evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death). | Safety Population | Posted | Number | Participants | From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months. |
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| Secondary | Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia) | Participants with a Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented by treatment cycle. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death). | Safety Population | Posted | Number | Participants | From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) Disease | AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented. | Safety Population | Posted | Number | Participants | From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study | Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products are counted in this table. | Safety Population | Posted | Number | Participants | From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 28.9 months) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM | Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Safety Population. | Posted | Mean | Standard Deviation | Gram per liter | From start of treatment up to 30 days after last treatment |
|
Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 111 months
All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 111 months.
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 | Chlorambucil | Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. | 99 | 227 | 57 | 227 | 175 | 227 |
| EG001 | Ofatumumab 1000 mg + Chlorambucil | Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. | 84 | 217 | 53 | 217 | 183 | 217 |
| EG002 | Total | All patients. | 183 | 444 | 110 | 444 | 358 | 444 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Autoimmune haemolytic anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Eosinophilia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Haemolysis | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Atrioventricular block complete | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Inflammation | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Vascular stent restenosis | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Hepatitis cholestatic | Hepatobiliary disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Anal abscess | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Empyema | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Haemophilus infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Neutropenic sepsis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Pharyngitis bacterial | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Pneumococcal sepsis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Pneumonia legionella | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Pneumonia staphylococcal | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Tuberculosis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
| |
| Injury | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
| |
| Traumatic ulcer | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA (19.0) | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA (19.0) | Systematic Assessment |
| |
| Mycobacterium test | Investigations | MedDRA (19.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Adenocarcinoma pancreas | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Systematic Assessment |
| |
| Central nervous system haemorrhage | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cerebellar ischaemia | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Extrapyramidal disorder | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Intracranial haematoma | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Bronchiectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Acute febrile neutrophilic dermatosis | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Peripheral artery stenosis | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Disclosure Office | Novartis Pharmaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D002699 | Chlorambucil |
| D013607 | Tablets |
| C527517 | ofatumumab |
| ID | Term |
|---|---|
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
| Male |
|
| American Indian or Alaskan Native |
|
| Asian - Central/South Asian Heritage |
|
| Asian - Mixed Race |
|
| White |
|
| OG001 | Ofatumumab + Chlorambucil | Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
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| Units |
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| Counts |
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| Participants |
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| Participants |
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| Ofatumumab + Chlorambucil |
Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
|
|
| Ofatumumab + Chlorambucil |
Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
|
|
Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
|
|
|
| OG001 | Ofatumumab + Chlorambucil | Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
|
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|
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Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle up to 12 cycles in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for up to 12 cycles.
|
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|
| OG001 | Ofatumumab + Chlorambucil | Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. |
|
|
|
|
Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
|
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| Counts |
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| Participants |
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