Ofatumumab Maintenance Treatment vs No Further Treatment in Relapsed CLL Responding to Induction Therapy
Condition: Leukaemia, Lymphocytic, Chronic
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Ofatumumab; Observation
Intervention description: Ofatumumab for maintenance therapy as IV infusions every 8 weeks . The first dose was 300 mg followed 1 week later by 1000 mg and 1000 mg every 8 weeks thereafter for up to 2 years.; Observation/Safety Evaluation
Intervention MeSH terms: Ofatumumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)
Enrollment: 480.0
Sex: All
Healthy volunteers: No
Keywords: maintenance therapy; anti-CD20 monoclonal antibody; ofatumumab

Summary:

      The purpose of this study was to determine if maintenance therapy with ofatumumab would
      prolong remission in patients with CLL who have responded to second or third line treatment.
      This study would also evaluate the safety of ofatumumab maintenance compared to observation
      (the current standard of care). This study was co-developed with the HOVON and NORDIC CLL
      group and would be conducted as a collaborative effort with GSK.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults with documented diagnosis of CLL based on the modified IWCLL updated NCI-WG
             guidelines (Hallek, 2008)

          -  At least PR according to the revised 2008 NCI-WG CLL criteria, within 3 months of the
             response assessment after the last dose of 2nd/3rd line treatment

          -  The anti-leukemic treatment before study entry should have been at least 3 months or 3
             cycles

          -  ECOG Performance Status of 0-2

          -  Signed written informed consent prior to performing any study-specific procedures

        Exclusion Criteria:

          -  Known primary or secondary fludarabine-refractory subjects, defined as treatment
             failure (failure to achieve a CR or PR) or disease progression within 6 months

          -  Prior maintenance therapy

          -  Known transformation of CLL (eg.Richter's transformation), prolymphocytic leukemia
             (PLL), or CNS involvement of CLL

          -  Active Autoimmune hemolytic anemia (AIHA) requiring treatment except if in the opinion
             of the investigator and medical monitor it is thought not to affect the subject's
             safety, the conduct of the study or the interpretation of the data

          -  Previous autologous or allogeneic stem cell transplantation

          -  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 B or C

          -  Other past or current malignancy (with the exception of basal cell carcinoma or the
             skin or in situ carcinoma of the cervix or breasts) unless the tumor was successfully
             treated with curative intent at least 2 years prior to trial entry except if in the
             opinion of the investigator and medical monitor it is thought not to affect the
             subject's safety, the conduct of the study or the interpretation of the data

          -  Clinically significant cardiac disease, including unstable angina, acute myocardial
             infarction within 6 months prior to screening, congestive heart failure, and
             arrhythmia requiring therapy, with the exception of exta systoles or minor conduction
             abnormalities except if in the opinion of the investigator and medical monitor it is
             thought not to affect the subject's safety, the conduct of the study or the
             interpretation of the data

          -  History of significant cerebrovascular disease or event with symptoms or sequelae

          -  Significant concurrent, uncontrolled medical condition that in the opinion of the
             investigator or GSK medical monitor contraindicates participation in this study

          -  Other anti-leukemic use of medications including glucocorticoids

          -  Known HIV positive

          -  Screening laboratory values: platelets <50 x 10x9/L, neutrophils<1.0 x 10x9/L,
             Creatinine > 1.5 X upper normal limit (unless normal creatinine clearance), total
             bilirubin >1.5 X upper normal limit, ALT >2.5 X upper normal limit (unless due to
             liver involvement of CLL), alkaline phosphase > 2.5 X upper normal limit

          -  Known or suspected hypersensitivity to ofatumumab that in the opinion of the
             investigator or medical monitor contraindicates study participation

          -  Subjects who have received treatment with any non-marketed drug substance or
             experimental therapy within 5-terminal half-lives or 4 weeks whichever is longer prior
             to first dose of study medication or currently participating in any other
             interventional clinical study

          -  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 ofatumumab dose. Adequate contraception is defined as abstinence, oral
             hormonal birth control, implants of levonorgestrel, estrogenic vaginal ring,
             percutaneous contraceptive patches, intrauterine device, and male partner
             sterilization if male partner is sole partner for that subject. For females in the
             USA, the use of a double barrier method is also considered adequate (condom or
             occlusive cap plus spermicidal agent).