A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia
Condition: Leukaemia, Lymphocytic, Chronic
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: chlorambucil, tablets; ofatumumab (GSK1841157) infusion
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; iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;
Intervention MeSH terms: Ofatumumab; Chlorambucil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      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).
    

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).