A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia
Condition: Leukaemia, Lymphocytic, Chronic
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: ofatumumab 100 mg, 1000 mg / vial
Intervention description: ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg
Intervention MeSH terms: Ofatumumab
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:

      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 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).