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A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01077622
First received: February 25, 2010
Last updated: October 31, 2013
Last verified: February 2012
  Purpose

Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect.

This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks.

Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population.

10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.


Condition Intervention Phase
Leukaemia, Lymphocytic, Chronic
Drug: ofatumumab 100 mg, 1000 mg / vial
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With a Dose-limiting Toxicity (DLT) [ Time Frame: Up to Week 8 ] [ Designated as safety issue: No ]
    A DLT was defined as the following toxicological findings, according to the Common Terminology Criteria for Adverse Events (AE) v3.0: any treatment-related Grade (G) >=3 non-hematotoxic AE, occurrence of G3 infusion reaction (treatment-related AE) at the day of infusion in a participant who received pre-medication or appropriate management during infusion (glucocorticoid) (the severity of the AE must have remained as >= G3 until the next day); and any of following: >= G4 hematotoxic treatment-related AEs (neutropenia lasting 7 days or more, febrile neutropenia).

  • Percentage of Participants (Par.) With Objective Response (OR), Defined as Complete Remission (CR), CR Incomplete (CRi), Partial Remission (PR), and Nodular PR (nPR) as Assessed by a Safety and Evaluation Review Committee (SERC) and the Investigator [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Par. were evaluated in accordance with the National Cancer Institute-sponsored Working Group. CR: no lymphadenopathy (Ly)/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils >=1.5*10^9/liter (L), platelets >100*10^9/L, hemoglobin >11.0 grams/deciliter, lymphocytes (LC) <4.0*10^9/L, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to chronic lymphocytic leukemia but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen, etc. nPR: nodules in BM.


Secondary Outcome Measures:
  • Progression-free Survival (PFS) as Assessed by a SERC [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    PFS is defined as the time from the start of treatment to the first documented sign of progressive disease (PD) or death due to any cause (whichever occurs earlier).

  • Duration of Response as Assessed by a SERC [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Duration of response is defined as the time from the first documented evidence of PR or better until the first documented sign of PD or death due to any reason in participants with PR or better.

  • Overall Survival [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from the first infusion of investigational drug to death due to any cause.

  • Time to Response as Assessed by a SERC [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Time to response is defined as the time from the first infusion of investigational drug to the first response (PR or better).

  • Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy as Assessed by a SERC [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Time to next CLL therapy is defined as the time from the first infusion of investigational drug to the first administration of the next CLL treatment. CLL therapy includes anti-cancer chemotherapy, anti-cancer radiotherapy, radio-immunotherapy, and antibody therapy.

  • Mean Laboratory Data for Hemoglobin at the Indicated Weeks as Assessed by the Investigator [ Time Frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Blood samples of the participants were collected for the assessment of hemoglobin.

  • Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by the Investigator [ Time Frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Blood samples of the participants were collected for the assessment of lymphocytes.

  • Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by the Investigator [ Time Frame: Weeks 8, 16, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Bone marrow (BM) aspiration was performed, and the bone marrow smears were prepared for the assessment of lymphocytes in the BM.

  • Mean Laboratory Data for Total Neutrophils (Total Absolute Neutrophil Count [ANC]) at the Indicated Weeks as Assessed by the Investigator [ Time Frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Blood samples of the participants were collected for the assessment of total neutrophils.

  • Mean Laboratory Data for Platelet Count at the Indicated Weeks as Assessed by the Investigator [ Time Frame: Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Blood samples of the participants were collected for the assessment of platelets.

  • Percentage of Bone Marrow Infiltration at the Indicated Weeks as Assessed by a SERC [ Time Frame: Weeks 8, 16, 24, 36, and 48 ] [ Designated as safety issue: No ]
    SERC assessed bone marrow infiltration with the bone marrow smears of participants provided by trial sites.

  • Mean Laboratory Data for Lymphocytes at the Indicated Weeks as Assessed by a SERC [ Time Frame: Weeks 8, 16, 24, 36, and 48 ] [ Designated as safety issue: No ]
    SERC assessed lymphocytes based on the data provided by trial sites.

  • Mean Laboratory Data for Lymphocytes as a Percentage in the Bone Marrow at the Indicated Weeks as Assessed by a SERC [ Time Frame: Weeks 8, 16, 24, 36, and 48 ] [ Designated as safety issue: No ]
    SERC assessed lymphocytes in the bone marrow (BM) based on the data with BM smears provided by trial sites.

  • Mean Laboratory Data for Total Neutrophils (Total ANC) at the Indicated Weeks as Assessed by a SERC [ Time Frame: Weeks 8, 16, 24, 36, and 48 ] [ Designated as safety issue: No ]
    SERC assessed total neutrophils based on the data provided by trial sites.

  • Number of Peripheral Blood Cluster of Differentiation (CD) CD19+ CD20+ Cells [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    CD19+ CD20+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.

  • Number of Peripheral Blood CD20+ CD23+ Cells [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    CD20+ CD23+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.

  • Number of Peripheral Blood CD19+ CD23+ Cells [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    CD19+ CD23+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.

  • Number of Peripheral Blood CD19+ CD5+ Cells [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    CD19+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.

  • Number of Peripheral Blood CD20+ CD5+ Cells [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    CD20+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.

  • Number of Peripheral Blood CD23+ CD5+ Cells [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    CD23+ CD5+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus.

  • Ratio of Immunoglobulin (Ig) Kappa/Ig Lambda [ Time Frame: Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Peripheral blood Ig kappa and Ig lambda were measured using flow cytometry. Abnormality of a ratio of Ig kappa and Ig lambda indicates clonality of lymphocytes. A normal range of this parameter is between 1.0 and 3.2.

  • Number of Participants With the Indicated Shift From Baseline (BL) in Night Sweats at the Indicated Weeks [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Night sweats are one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had night sweats at BL, and still had night sweats at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had night sweats at BL, but did not have night sweats at Week 1 are represented in the BL, yes; Week 1, no category.

  • Number of Participants With the Indicated Shift From Baseline (BL) in Weight Loss at the Indicated Weeks [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Weight loss is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had weight loss at BL, and still had weight loss at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had weight loss at BL, but did not have weight loss at Week 1 are represented in the BL, yes; Week 1, no category.

  • Number of Participants With the Indicated Shift From Baseline (BL) in Fever at the Indicated Weeks [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Fever is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had fever at BL, and still had fever at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had fever at BL, but did not have fever at Week 1 are represented in the BL, yes; Week 1, no category.

  • Number of Participants With the Indicated Shift From Baseline (BL) in Extreme Fatigue at the Indicated Weeks [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    Extreme fatigue is one of the clinical characteristics of CLL. B symptoms are systemic symptoms of fever, night sweats, weight loss, and extreme fatigue, which can be associated with CLL. Participants who had extreme fatigue at BL, and still had extreme fatigue at Week 1, for example, are represented in the BL, yes; Week 1, yes category. Participants who had extreme fatigue at BL, but did not have extreme fatigue at Week 1 are represented in the BL, yes; Week 1, no category.

  • Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Weeks 8, 24, and 48 [ Time Frame: Baseline and Weeks 8, 24, and 48 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Tested Positive/Negative for Human Anti-human Antibodies (HAHA) at Screening and at Weeks 24 and 48 [ Time Frame: Screening; Weeks 24 and 48 ] [ Designated as safety issue: No ]
    HAHA are indicators of immunogenicity to ofatumumab.

  • Number of Participants With a Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 28, 36, and 48 ] [ Designated as safety issue: No ]
    ECOG PS is used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. The grades for the scale range from 0 (fully active) to 4 (completely disabled), with increasing severity.

  • Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    Blood sampling on Day 1 and at Weeks 7 and 24 for pharmacokinetic (PK) evaluation was performed at the following time points: 0.5 hour (hr) before infusion; end of infusion; and 10 minutes (min), 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.

  • Minimum Plasma Concentration (Cmin) of Ofatumumab [ Time Frame: Weeks 7 and 24 ] [ Designated as safety issue: No ]
    Blood sampling at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.

  • Time to Reach Cmax (Tmax) Following Ofatumumab Administration [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.

  • Half-life (t1/2) of Ofatumumab [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    t1/2 of ofatumumab is the time required for the plasma concentration of ofatumumab to decrease by half. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.

  • Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for Ofatumumab [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    AUC(0-t) was evaluated from the plasma concentration versus time curve from time zero to the last measurable time point (time t). Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.

  • Area Under the Plasma Concentration-time Curve From Time Zero to 168 hr (AUC[0-168]) for Ofatumumab at Week 7 [ Time Frame: Week 7 ] [ Designated as safety issue: No ]
    Blood sampling at Week 7 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.

  • Area Under the Plasma Concentration-time Curve From Time Zero to 672 hr (AUC[0-672]) for Ofatumumab at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Blood sampling at Week 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), 120 hr (5 days), 168 hr (7 days), and 336 hr (14 days) after infusion of ofatumumab.

  • Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.

  • Clearance (CL) of Ofatumumab From Plasma [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    CL of ofatumumab from plasma of participants was evaluated. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.

  • Volume of Distribution (Vz) During the Terminal Phase for Ofatumumab [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    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. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.

  • Volume of Distribution at Steady State (Vss) for Ofatumumab [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    Vss for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body in equilibrium conditions to steady-state plasma concentrations. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.

  • Mean Residence Time (MRTinf) of Ofatumumab [ Time Frame: Day 1; Weeks 7 and 24 ] [ Designated as safety issue: No ]
    MRTinf is the average amount of time that ofatumumab spends in the body. Blood sampling on Day 1 and at Weeks 7 and 24 for PK evaluation was performed at the following time points: 0.5 hr before infusion; end of infusion; and 10 min, 1 hr, 2 hr, 24 hr (1 day), 72 hr (3 days), and 120 hr (5 days) after infusion of ofatumumab. At Weeks 7 and 24, blood sampling was also performed 168 hr (7 days) and 336 hr (14 days) after infusion of ofatumumab.


Other Outcome Measures:
  • Serum Hemolytic Complement Titer at Weeks 36 and 48: CH50 [ Time Frame: Weeks 36 and 48 ] [ Designated as safety issue: No ]
    The CH50 is the serum complement to lyse 50% of sensitized red blood cells; it's 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.


Enrollment: 10
Study Start Date: September 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2000 mg dose
ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg
Drug: ofatumumab 100 mg, 1000 mg / vial
ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg

Detailed Description:

Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect.

This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks.

Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population.

10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects eligible for enrolment in the study must meet all of the following criteria at the time of screening:

  • Patients who gave consent to this study participation and signed into informed consent form.
  • Previously treated(Patients who received at least one prior CLL therapy and have either relapsed or have refractory disease, both requiring therapy.) CLL with at least 5 x 109 B lymphocytes/ L (5000/μL). The diagnosis of CLL requires CD5, CD19, CD20 and CD23 positivity, according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines [Hallek, 2008].
  • Laboratory test values meet the following criteria which indicate that patients have sufficient physiological functions;

Neutrophils:1≥ 500 /mm3 ALT ≤ 2.5 times upper local normal limit Creatinine ≤ 1.5 times upper local normal limit Total bilirubin≤ 1.5 times upper local normal limit

1:Patients should not receive any hematopoietic cytokine such as G-CSF preparations within 1 week before screening laboratory test for neutrophil counting.

- Patients who passed the following periods from the last anti-cancer treatments at the time of screening: At least 4 weeks after anti-cancer chemotherapy. At least 4 weeks after anti-cancer radiotherapy. At least 4 weeks after glucocorticoids treatment for CLL unless ≤ 10 mg of prednisolone /day.

At least 12 weeks after radio-immunotherapy and/or antibody therapy.

  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.
  • Life expectancy more than 24 weeks after screening test.
  • Aged ≥ 20 (at the time of signing informed consent).
  • 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:

A subject will not be eligible for inclusion in this study if any of the following criteria is met:

  • Active malignancy which needs therapy with anti-cancer drug, except for CLL.
  • Known Richter's transformation.
  • Previous autologous stem cell transplantation, within 24 weeks prior to screening.
  • Previous allogenic stem cell transplantation.
  • Known CNS involvement.
  • History of significant cerebrovascular disease.
  • Current cardiac disease requiring medical treatment (e.g. atrial flutter treated with acetylsalicylic acid and beta blocking agents).
  • Chronic or active infectious disease requiring systemic (intravenous or oral) treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.
  • Suspected/known immediate or delayed hypersensitivity to components of ofatumumab.
  • Patients previously treated with ofatumumab.
  • Positive serology test for any of HBsAg, anti-HBcAb or anti-HCVAb. If only anti-HBcAb results is positive, HBV-DNA test will be performed. If HBV-DNA results in negative, the patient is eligible.
  • HIV positivity.
  • Pregnant or lactating women.
  • Women of childbearing potential not willing to use adequate contraception during the study and one year after the last dose of ofatumumab, and male patients not willing to use adequate contraception during the study. Adequate contraception is defined as follows but not limited to; Abstinence. Oral Contraceptive (exclude oral progesterone alone). Intrauterine device (IUD) or intrauterine system (IUS). Male partner sterilization. Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (gel / film) etc.
  • Use of an investigational drug within 4 weeks prior to screening.
  • Current participation in any other clinical study.
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
  • Patients who an investigator (or sub investigator) judges ineligible to this study.

Note; Child-bearing potential: a woman with functioning ovaries and uterine, or no documented sterility (i.e., a woman with functioning ovaries who have a current documented tubal ligation, women who have had a hysterectomy, women who are post-menopausal, or women who have had both ovaries surgically removed).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01077622

Locations
Japan
GSK Investigational Site
Aichi, Japan, 466-8650
GSK Investigational Site
Kanagawa, Japan, 259-1143
GSK Investigational Site
Nagasaki, Japan, 852-8501
GSK Investigational Site
Tokyo, Japan, 135-8550
GSK Investigational Site
Tokyo, Japan, 104-0045
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 138-736
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01077622     History of Changes
Other Study ID Numbers: 112758
Study First Received: February 25, 2010
Results First Received: December 21, 2011
Last Updated: October 31, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 24, 2014