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A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

Primary Purpose

Leukaemia, Lymphocytic, Chronic

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

chlorambucil, tablets

ofatumumab (GSK1841157) infusion

About this trial

This is an interventional treatment trial for Leukaemia, Lymphocytic, Chronic

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of CLL defined by : Circulating B lymphocytes ≥5,000 /μL AND Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, and CD23 prior to Visit 2.
Considered inappropriate for fludarabine-based therapy
Active disease and indication for treatment based on modified NCI-WG guidelines defined by presenting at least any one of the following conditions :

Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia.

Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.

Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.

Progressive lymphocytosis with an increase of more than 50% over a two month period or an lymphocyte doubling time of less than 6 months.

A minimum of any one of the following disease-related symptoms must be present : a) Unintentional Weight loss ≥ 10% within the previous six months ; b) Fevers >38.0 degree C for ≥ 2 weeks without evidence of infection ; or c) Night sweats for more than 1 month without evidence of infection.

Not been previously treated for CLL (prior autoimmune hemolytic anemia treatment permitted).
ECOG Performance Status of 0-2.
Life expectancy of at least 6 months, in the opinion of the investigator.
Age ≥ 20 years.
Signed written informed consent prior to performing any study-specific procedures.
Patients possible to stay at the trial site for at least two days (the day of the first infusion and a subsequent day).

Exclusion Criteria:

Prior immuno- or chemotherapy for CLL or small lymphocytic lymphoma (SLL) with any agent except corticosteroids used to treat autoimmune hemolytic anemia.
Previous autologous or allogeneic stem cell transplantation.
Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy > 100 mg/day equivalent to hydrocortisone, or chemotherapy.
Known transformation of CLL (e.g. Richter).
Known CNS involvement of CLL.
Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to screening (Visit 1), congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.
History of significant cerebrovascular disease or event with significant symptoms or sequelae*.
Glucocorticoid use, unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) for <7 days for exacerbations other than CLL (e.g. asthma).
Known HIV positive.
Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb and/or HBsAb positive, an HBV DNA test will be performed and if positive the subject will be excluded.
Screening laboratory values :

Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance). Total bilirubin > 2.0 times upper normal limit (unless due to Gilbert's syndrome).

Alanine transaminase (ALT) > 3.0 times upper normal limit.

Previous treatment or known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor is a contraindication to their participation in the present study.
Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to Visit 1, whichever is longer, treatment with any anti-CD20 monoclonal antibody within 3 months of Visit 1, or participation in any other interventional clinical study. Note: Participation in any other interventional clinical study after disease progression during post PD-follow-up is permitted.
Known or suspected inability to comply with study protocol.
Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last treatment dose. Adequate contraception is defined as oral hormonal birth control, intrauterine device, male partner sterilization (if male partner is sole partner for that subject) and the double barrier method (condom or occlusive cap plus spermicidal agent).

Sites / Locations

GSK Investigational Site
GSK Investigational Site
GSK Investigational Site
GSK Investigational Site
GSK Investigational Site
GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ofatumumab + chlorambucil

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Participants Who Developed Toxicity Requiring Discontinuation From Study Treatment During Cycle 1

Tolerability of ofatumumab in combination with chlorambucil was evaluated based on the number of participants who developed toxicity requiring discontinuation from study treatment during Cycle 1. The treatment was considered tolerable when 0 of 3 participants, or <=2 of 6 participants developed toxicity which required discontinuation of study treatment during Cycle 1. The toxicity requiring discontinuation was determined based on the pre-defined withdrawal criteria.

Number of Participants With Overall Response, as Assessed by the Independent Review Committee (IRC) With CT, IRC and Investigator

Response evaluated as per International Workshop for Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-sponsored Working Group (NCI-WG) Guidelines, 2008. Overall response rate (ORR) is defined as percentage of par. achieving complete remission (CR), nodular partial remission (nPR), CR-incomplete (CRi) or PR. CR (>=2 months after last treatment): lymphocytes (LC) <4000 per microliter (μL), no lymphadenopathy (Ly)>1.5 cm/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils (N)>1500/µL, platelets (PL)>100,000/µL, hemoglobin (Hb)>11 grams/deciliter (g/dL), bone marrow (BM) sample must be normocellular for age,<30% LC, no lymphoid nodule (LN). PR:>=50% decrease in LC, Ly, size of liver and spleen; and at least one of these: N>1500/μL, PL>100,000/µL or 50% improvement over Baseline (BL), Hb>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.

Secondary Outcome Measures

Number of Participants With CR, as Assessed by the IRC, IRC With CT, and the Investigator

Response was determined according to the IWCLL updated NCI-WG guidelines, 2008. According to the guidelines, CR (all the criteria at least 2 months after last treatment): peripheral blood lymphocytes below < 4,000/μL, no Ly > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; Neu >1500 /µL, PL >100,000/µL, Hb >11 g/dL, BM sample must be normocellular for age, <30% lymphocytes, no LN. PR: >=50% decrease in peripheral blood lymphocytes, Ly, size of liver and spleen; and blood count showing at least one of the following results: Neu>1500/μL, PL >100,000/µL or 50% improvement over BL, Hb >11 g/dL or 50% improvement over BL. No increase in LN and no new LN.

Progression-free Survival (PFS), as Assessed by the IRC and the Investigator

Progression free survival is defined as the time from start of treatment until disease progression (PD) or death due to any cause. PD was determined by the IRC or investigator according to the definitions of response in the IWCLL updated NCI-WG guidelines, 2008. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [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 per microliter B-lymphocytes; transformation to a more aggressive histology; or occurrence of cytopenia attributable to chronic lymphocytic leukemia. PFS was censored at the last visit with adequate assessment for participants who were alive and had not progressed.

Overall Survival

Overall survival is defined as time from start of treatment until death due to any cause. For participants who did not die, time to death was censored at the time of the last date of contact.

Time to Response, as Assessed by the IRC

Time to response is defined as the time from start of treatment until the first response (CR/CRi/nPR/PR). Response was determined according to the IWCLL updated NCI-WG guidelines, 2008. This analysis only included participants who had a response while in the study, there was no censoring.

Duration of Response, as Assessed by the IRC

Duration of response is defined as the time from the first documented evidence of CR, CRi, nPR or PR until the first documented sign of PD or death in participants with CR, CRi, nPR or PR. For participants who did not progress or die, duration of response was censored on the date of last assessment.

Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy

Time to next CLL therapy is defined as the time from start of treatment until the first administration of the next CLL treatment other than chlorambucil administrations scheduled in this study. Time to next CLL therapy was restricted to the subgroup of the population who receive a next CLL therapy after experiencing disease progression.

Number of Participants With no B-symptoms (Constitutional Symptoms) and With at Least One B-symptom (Constitutional Symptoms) at the Indicated Time Points

The number of participants with no B-symptoms (no night sweat [without signs of infection], no unexplained, unintentional weight loss >= 10% within the previous 6 months, no recurrent, unexplained fever of greater than 38 degrees celcius for 2 weeks and no extreme fatigue) and the number of participants with at least one of the B-symptoms are summarized by assessment time. The presence of the B-symptoms was assessed at Baseline, Day 1 of each treatment cycle and follow-up (FU). Baseline was the last pre-dose assessment performed at Cycle (C) 1-Day (D) 1.

Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

ECOG PS is a scale to assess disease progression, extent to which disease affects the daily living abilities and determines appropriate treatment and prognosis. It is scored on a scale of 0 to 5 as, 0 (fully active), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2 (ambulatory and capable of all self cares but unable to carry out any work activities, up and about > 50% of waking hours), 3 (capable of only limited self cares, confined to bed or chair > 50% of waking hours), 4 (completely disabled, cannot carry on any self cares, totally confined to bed or chair), 5 (death). Improvement is defined as decrease from Baseline by at least one step on the ECOG performance status scale (yes/no). Baseline was the last pre-dose assessment performed on Cycle 1-Day 1(C1-D1). When C1-D1 was missing, the last assessment performed prior to pre-dose C1-D1 was used. It was performed on Day 1 of each cycle and follow-up (FU).

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 important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed.

Number of Participants With AEs of Maximum Severity

Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events

Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.03 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death). AEs not in the list of CTCAE were graded at discretion of the investigator. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. Participants with Grade (G)3 or G4 adverse event of infection and myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented. Also presented are number of participants with autoimmune hemolytic anemia (AIHA). 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.

Number of Participants With the Indicated Results for Human Anti-human Antibody (HAHA) at the Indicated Time Points

HAHA are indicators of immunogenicity induced by ofatumumab. Blood samples were taken from participants at Screening, Cycle 4-Day 85, FU 1-PDFU 1, and FU 169-PDFU 169. The presence of HAHA in human serum was determined using a validated electrochemiluminescent assay in a multi-tier assay format. The results are presented as participants with HAHA results as positive, negative or confirmation required.

Mean Change From Baseline in the Immunoglobulins (Ig) Antibodies IgA, IgG, and IgM at the Indicated Time Points

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. Immunoglobulins were measured at Cycle 1-Day 1, FU 1-PDFU 1, and FU 169-PDFU 169 for participants in CR, PR, and stable disease (SD).

Number of Participants Who Were Positive or Negative for Minimal Residual Disease (MRD), as Assessed by IRC With CT

MRD refers to small number of leukemic cells that remain in the participant's body during treatment or after treatment in participants who achieved a confirmed complete remission. MRD assessment in bone marrow aspiration sample was perfrmed by flow cytometry (cluster of differentiation [CD]5, CD19, CD20, CD23). The absence of MRD was defined as less than one CLL cell per 10,000 leukocytes. The number of participants who were positive and negative for MRD are presented.

Change From Baseline in CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points

CD5+CD19+ cells were counted in peripheral blood by flow cytometry. Baseline CD5+CD19+ and CD5-CD19+ cell count value is 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. B-cell monitoring (CD5+CD19+ and CD5-CD19+) was performed at Cycle 1 (Day 1, Day 15) and Cycle 2 (Day 29, Day 43), on Day 1 of Cycle 3, 4, 5, 6, 9 and 12 (Day 57, Day 85, Day 113, Day 141, Day 225, Day 309), 28 days after the first day of the last treatment cycle (FU 1-PDFU 1) for all participants depending on the number of cycles administered, and 84 and 168 days after the day of FU 1-PDFU 1 for participants in CR, PR, and SD.

Beta-2 Microglobulin at Cycle 1-Day 1

Beta-2-microglobulin is a protein present on the surface of most cells. Higher levels indicate a poor prognosis of CLL. Beta-2 microglobulin was measured at Cycle 1-Day 1.

Complement (CH50) at Cycle 1-Day 1 and Cycle 4-Day 85

The CH50 is the serum complement to lyse 50% of sensitized red blood cells; it is a marker of complement activation. A high CH50 level suggests evidence for complement activation, whereas a low CH50 level suggests lack of complement activation. Peripheral blood samples were collected for analysis at Cycle 1-Day 1 and Cycle 4-Day 85.

Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab

Maximum (peak) plasma drug concentration of ofatumumab was determined at Cycle 1-Day 1 and Cycle 3-Day 57. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr), and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).

Cmax of Serum Chlorambucil

Cmax of serum chlorambucil was assesed at Cycle 1-Day 1, Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Cmax of Serum Phenyl Acetic Acid Mustard

Cmax of chlorambucil metabolite phenyl acetic acid mustard was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Minimum Plasma Concentration (Cmin) of Ofatumumab

Minimum plasma drug concentration of ofatumumab was determined at Cycle 1-Day 8, Cycle 2-Day 29, Cycle 3-Day 57, Cycle 4-Day 85, Cycle 5-Day 113, and Cycle 6-Day 141. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr), Cycle 2-Day 29 (pre-dose), Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr), Cycle 4-Day 85 (pre-dose, 30 min post end of infusion), Cycle 5-Day 113 (pre-dose and end of infusion) and Cycle 6-Day 141 (pre-dose and end of infusion).

Cmin of Chlorambucil

Cmin of chlorambucil was assesed at Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Cmin of Phenyl Acetic Acid Mustard

Cmin of chlorambucil metabolite phenyl acetic acid mustard was assesed at Cycle 1-Day 4 and Cycle 3-Day 57. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

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 at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

Area Under the Drug Plasma Concentration-time Curve From Dosing to Time Tau (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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. For ofatumumab it was assesed at Cycle 1-Day 1 and Cycle 3-Day 57. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).

AUC(0-tau) of Chlorambucil

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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. It was assesed at 1st (Cycle 1-Day 1), 4th (Cycle 1-Day 4), and 15th (Cycle 3-Day 57) chlorambucil administration. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

AUC(0-tau) of Phenyl Acetic Acid Mustard

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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. It was assesed at 1st (Cycle 1-Day 1), 4th (Cycle 1-Day 4), and 15th (Cycle 3-Day 57) chlorambucil administration. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab

The total AUC or AUC0-infinity is the area under the curve from time 0 extrapolated to infinite time. It was assesed on Cycle 1-Day 1. The samples were collected at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

AUC(0-infinity) for Chlorambucil

The total AUC or AUC0-infinity is the area under the curve from time 0 extrapolated to infinite time. It was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

AUC(0-infinity) for Phenyl Acetic Acid Mustard

The total AUC or AUC(0-infinity) is the area under the curve from time 0 extrapolated to infinite time. It was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

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. Samples were collected at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

Plasma Half-life (t1/2) of Ofatumumab

t1/2 is the time required for the plasma concentration of ofatumumab to decrease by half. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).

Plasma Half-life (t1/2) of Chlorambucil

t1/2 is the time required for the serum concentration of chlorambucil to decrease by half. Blood samples for serum concentration of chlorambucil was collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Plasma Half-life (t1/2) of Phenyl Acetic Acid Mustard

t1/2 is the time required for the plasma/serum concentration of phenylacetic acid mustard to decrease by half. Blood samples for serum concentration of phenylacetic acid mustard was collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Time to Maximum Concentration (Tmax) of Ofatumumab

Tmax is the time required for reaching maximum concentration of drug (Cmax). Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).

Time to Maximum Concentration (Tmax) of Chlorambucil

Tmax is the time required for reaching maximum concentration of drug (Cmax). Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Time to Maximum Concentration (Tmax) of Phenyl Acetic Acid Mustard

Mean Residence Time to Infinity (MRTinf) of Ofatumumab

MRTinf is the average amount of time that ofatumumab spends in the body. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

Mean Residence Time Inf (MRTinf) of Chlorambucil

MRTinf is the average amount of time that chlorambucil spends in the body. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Mean Residence Time Inf (MRTinf) of Phenyl Acetic Acid Mustard

MRTinf is the average amount of time that phenyl acetic acid mustard spends in the body. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Volume of Distribution (Vz) of Ofatumumab

Vz for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body during the terminal phase to the plasma concentration during the terminal phase. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

Apparent Total Clearance of the Drug From Plasma (CL/F) for Chlorambucil

CL/F is defined as the apparent total clearance of the drug from plasma after oral administration of chlorambucil. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Apparent Volume of Distribution During Terminal Phase (Vz/F) of Chlorambucil

Vz/F of chlorambucil is defined as the apparent volume of distribution during terminal phase after non-intravenous (oral) administration of chlorambucil. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

%AUC_extrap of Ofatumumab

%AUC_extrap is defined as the area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr).

%AUC_extrap of Chlorambucil

%AUC_extrap is defined as the area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

%AUC_extrap of Phenyl Acetic Acid Mustard

AUC (0-t) of Ofatumumab

AUC (0-t) represents the area under the concentration curve of ofatumumab in plasma from 0 to time t hours. AUC (0-t) was assessed at 168 hours and 672 hours post-dose.

AUC (0-t) of Chlorambucil

AUC (0-t) represents the area under the concentration curve of chlorambucil in serum from 0 to time t hours. AUC (0-t) was assessed at 6 hours and 24 hours.

AUC (0-t) of Phenyl Acetic Acid Mustard

AUC (0-t) represents the area under the concentration curve of phenyl acetic acid mustard in serum from 0 to time t hours. AUC (0-t) was assessed at 6 hours and 24 hours.

Dose Normalized Cmax (Cmax/D) for Chlorambucil

Cmax/D is defined as the maximum plasma concentration (Cmax) per unit dose. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Cmax/D for Phenyl Acetic Acid Mustard

Cmax/D is defined as the maximum plasma concentration (Cmax) per unit dose. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

AUC (0-6)/D, AUC(0-24)/D, AUC (0-inf)/D, and AUC (0-tau)/D of Chlorambucil

Dose adjusted AUC for the indicated time points were assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

AUC (0-6)/D, AUC(0-24)/D, AUC (0-inf)/D and AUC (0-tau)/D of Phenyl Acetic Acid Mustard

Full Information

NCT ID

NCT01563055

First Posted

March 15, 2012

Last Updated

July 16, 2015

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01563055

Brief Title

A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

Official Title

A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Completed

Study Start Date

April 2012 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Detailed Description

This is an open-label study to evaluate tolerability, safety, efficacy and pharmacokinetic profile of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated Chronic Lymphocytic Leukemia (CLL). Ofatumumab will be infused intravenously at Day 1 (300 mg) and Day 8 (1000 mg) in the first 28-day cycle, followed by infusions of 1000 mg at the first day of each 28-day cycle. Chlorambucil will be given 10 mg/m2 at Day 1-7 in each 28-day cycle. The primary objectives are to evaluate tolerability and overall response rate (ORR) of ofatumumab with chlorambucil for previously untreated (frontline) CLL. Secondary objectives include to evaluate complete remission (CR) rate, progression free survival (PFS), overall survival (OS), time to response, duration of response, time to next therapy, incidence and severity of adverse events and serious adverse events, incidences of grade 3 and 4 infections and myelosuppression (anemia, neutropenia, thrombocytopenia), and pharmacokinetics of ofatumumab and chlorambucil.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukaemia, Lymphocytic, Chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ofatumumab + chlorambucil

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

chlorambucil, tablets

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

ofatumumab (GSK1841157) infusion

Intervention Description

iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;

Primary Outcome Measure Information:

Title

Number of Participants Who Developed Toxicity Requiring Discontinuation From Study Treatment During Cycle 1

Description

Time Frame

From start of treatment through Cycle 1 (Week 4)

Title

Number of Participants With Overall Response, as Assessed by the Independent Review Committee (IRC) With CT, IRC and Investigator

Description

Time Frame

From start of treatment until disease progression or death (up to Week 62.3)

Secondary Outcome Measure Information:

Title

Number of Participants With CR, as Assessed by the IRC, IRC With CT, and the Investigator

Description

Time Frame

From start of treatment until disease progression or death (up to Week 62.3)

Title

Progression-free Survival (PFS), as Assessed by the IRC and the Investigator

Description

Time Frame

From start of treatment until disease progression or death (up to Week 62.3)

Title

Overall Survival

Description

Overall survival is defined as time from start of treatment until death due to any cause. For participants who did not die, time to death was censored at the time of the last date of contact.

Time Frame

From start of treatment until death (up to Week 62.3

Title

Time to Response, as Assessed by the IRC

Description

Time Frame

From start of treatment until the first response (CR/CRi/nPR/PR) (up to Week 62.3)

Title

Duration of Response, as Assessed by the IRC

Description

Time Frame

From initial response (CR/CRi/nPR/PR) until disease progression or death (up to Week 62.3)

Title

Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy

Description

Time Frame

From start of treatment until the first administration of the next CLL therapy (up to Week 62.3)

Title

Number of Participants With no B-symptoms (Constitutional Symptoms) and With at Least One B-symptom (Constitutional Symptoms) at the Indicated Time Points

Description

Time Frame

Baseline, C2-D29, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9 -D225, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), FU 85-PDFU 85 (84 days after FU-1), and FU 169-PDFU 169 (168 days after FU-1)

Title

Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Description

Time Frame

Title

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

Description

Time Frame

From start of treatment until follow-up for survival (up to Week 62.3)

Title

Number of Participants With AEs of Maximum Severity

Description

Time Frame

From start of treatment until follow-up for survival (up to Week 62.3)

Title

Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events

Description

Time Frame

From start of treatment until follow-up for survival (up to Week 62.3)

Title

Number of Participants With the Indicated Results for Human Anti-human Antibody (HAHA) at the Indicated Time Points

Description

Time Frame

Screening, Cycle 4-Day 85, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), and FU 169-PDFU 169 (168 days after FU-1)

Title

Mean Change From Baseline in the Immunoglobulins (Ig) Antibodies IgA, IgG, and IgM at the Indicated Time Points

Description

Time Frame

Baseline (Cycle 1-Day 1), FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), and FU 169-PDFU 169 (168 days after FU-1)

Title

Number of Participants Who Were Positive or Negative for Minimal Residual Disease (MRD), as Assessed by IRC With CT

Description

Time Frame

FU 85-PDFU 85 (84 days after FU-1)

Title

Change From Baseline in CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points

Description

Time Frame

Baseline, C1-D15, C2-D29, C2-D43, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9-D225, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), FU 85-PDFU 85 (84 days after FU-1), and FU 169-PDFU 169 (168 days after FU-1)

Title

Beta-2 Microglobulin at Cycle 1-Day 1

Description

Beta-2-microglobulin is a protein present on the surface of most cells. Higher levels indicate a poor prognosis of CLL. Beta-2 microglobulin was measured at Cycle 1-Day 1.

Time Frame

Cycle 1-Day 1

Title

Complement (CH50) at Cycle 1-Day 1 and Cycle 4-Day 85

Description

Time Frame

Cycle 1-Day 1 and Cycle 4-Day 85

Title

Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab

Description

Time Frame

Cycle 1-Day 1 and Cycle 3-Day 57

Title

Cmax of Serum Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Cmax of Serum Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Minimum Plasma Concentration (Cmin) of Ofatumumab

Description

Time Frame

Cycle 1-Day 8, Cycle 2-Day 29, Cycle 3-Day 57, Cycle 4-Day 85, Cycle 5-Day 113, and Cycle 6-Day 141

Title

Cmin of Chlorambucil

Description

Time Frame

Cycle 1-Day 4 and Cycle 3-Day 57

Title

Cmin of Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 4 and Cycle 3-Day 57

Title

Total Plasma Clearance (CL) of Ofatumumab

Description

Time Frame

Cycle 1-Day 1

Title

Area Under the Drug Plasma Concentration-time Curve From Dosing to Time Tau (AUC[0-tau]) of Ofatumumab

Description

Time Frame

Cycle 1-Day 1 and Cycle 3-Day 57

Title

AUC(0-tau) of Chlorambucil

Description

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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. It was assesed at 1st (Cycle 1-Day 1), 4th (Cycle 1-Day 4), and 15th (Cycle 3-Day 57) chlorambucil administration. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

AUC(0-tau) of Phenyl Acetic Acid Mustard

Description

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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. It was assesed at 1st (Cycle 1-Day 1), 4th (Cycle 1-Day 4), and 15th (Cycle 3-Day 57) chlorambucil administration. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab

Description

Time Frame

Cycle 1-Day 1

Title

AUC(0-infinity) for Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

AUC(0-infinity) for Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Volume of Distribution at Steady State (Vss) of Ofatumumab

Description

Time Frame

Cycle 1-Day 1

Title

Plasma Half-life (t1/2) of Ofatumumab

Description

Time Frame

Cycle 1-Day 1 and Cycle 3-Day 57

Title

Plasma Half-life (t1/2) of Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Plasma Half-life (t1/2) of Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Time to Maximum Concentration (Tmax) of Ofatumumab

Description

Time Frame

Cycle 1-Day 1 and Cycle 3-Day 57

Title

Time to Maximum Concentration (Tmax) of Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Time to Maximum Concentration (Tmax) of Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Mean Residence Time to Infinity (MRTinf) of Ofatumumab

Description

MRTinf is the average amount of time that ofatumumab spends in the body. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

Time Frame

Cycle 1-Day 1

Title

Mean Residence Time Inf (MRTinf) of Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Mean Residence Time Inf (MRTinf) of Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Volume of Distribution (Vz) of Ofatumumab

Description

Time Frame

Cycle 1-Day 1

Title

Apparent Total Clearance of the Drug From Plasma (CL/F) for Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Apparent Volume of Distribution During Terminal Phase (Vz/F) of Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

%AUC_extrap of Ofatumumab

Description

Time Frame

Cycle 1-Day 1

Title

%AUC_extrap of Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

%AUC_extrap of Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

AUC (0-t) of Ofatumumab

Description

AUC (0-t) represents the area under the concentration curve of ofatumumab in plasma from 0 to time t hours. AUC (0-t) was assessed at 168 hours and 672 hours post-dose.

Time Frame

Cycle 1-Day 1 and Cycle 3-Day 57

Title

AUC (0-t) of Chlorambucil

Description

AUC (0-t) represents the area under the concentration curve of chlorambucil in serum from 0 to time t hours. AUC (0-t) was assessed at 6 hours and 24 hours.

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

AUC (0-t) of Phenyl Acetic Acid Mustard

Description

AUC (0-t) represents the area under the concentration curve of phenyl acetic acid mustard in serum from 0 to time t hours. AUC (0-t) was assessed at 6 hours and 24 hours.

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Dose Normalized Cmax (Cmax/D) for Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

Cmax/D for Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

AUC (0-6)/D, AUC(0-24)/D, AUC (0-inf)/D, and AUC (0-tau)/D of Chlorambucil

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Title

AUC (0-6)/D, AUC(0-24)/D, AUC (0-inf)/D and AUC (0-tau)/D of Phenyl Acetic Acid Mustard

Description

Time Frame

Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of CLL defined by : Circulating B lymphocytes ≥5,000 /μL AND Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, and CD23 prior to Visit 2. Considered inappropriate for fludarabine-based therapy Active disease and indication for treatment based on modified NCI-WG guidelines defined by presenting at least any one of the following conditions : Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia. Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly. Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. Progressive lymphocytosis with an increase of more than 50% over a two month period or an lymphocyte doubling time of less than 6 months. A minimum of any one of the following disease-related symptoms must be present : a) Unintentional Weight loss ≥ 10% within the previous six months ; b) Fevers >38.0 degree C for ≥ 2 weeks without evidence of infection ; or c) Night sweats for more than 1 month without evidence of infection. Not been previously treated for CLL (prior autoimmune hemolytic anemia treatment permitted). ECOG Performance Status of 0-2. Life expectancy of at least 6 months, in the opinion of the investigator. Age ≥ 20 years. Signed written informed consent prior to performing any study-specific procedures. Patients possible to stay at the trial site for at least two days (the day of the first infusion and a subsequent day). Exclusion Criteria: Prior immuno- or chemotherapy for CLL or small lymphocytic lymphoma (SLL) with any agent except corticosteroids used to treat autoimmune hemolytic anemia. Previous autologous or allogeneic stem cell transplantation. Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy > 100 mg/day equivalent to hydrocortisone, or chemotherapy. Known transformation of CLL (e.g. Richter). Known CNS involvement of CLL. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to screening (Visit 1), congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities. History of significant cerebrovascular disease or event with significant symptoms or sequelae*. Glucocorticoid use, unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) for <7 days for exacerbations other than CLL (e.g. asthma). Known HIV positive. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb and/or HBsAb positive, an HBV DNA test will be performed and if positive the subject will be excluded. Screening laboratory values : Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance). Total bilirubin > 2.0 times upper normal limit (unless due to Gilbert's syndrome). Alanine transaminase (ALT) > 3.0 times upper normal limit. Previous treatment or known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor is a contraindication to their participation in the present study. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to Visit 1, whichever is longer, treatment with any anti-CD20 monoclonal antibody within 3 months of Visit 1, or participation in any other interventional clinical study. Note: Participation in any other interventional clinical study after disease progression during post PD-follow-up is permitted. Known or suspected inability to comply with study protocol. Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last treatment dose. Adequate contraception is defined as oral hormonal birth control, intrauterine device, male partner sterilization (if male partner is sole partner for that subject) and the double barrier method (condom or occlusive cap plus spermicidal agent).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

466-8650

Country

Japan

Facility Name

GSK Investigational Site

City

Hokkaido

ZIP/Postal Code

060-8543

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

259-1143

Country

Japan

Facility Name

GSK Investigational Site

City

Kyoto

ZIP/Postal Code

602-8566

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

104-0045

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

135-8550

Country

Japan

12. IPD Sharing Statement

Learn more about this trial

A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

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