Ofatumumab vs Physician's Choice in Subjects With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia
Condition: Leukaemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Ofatumumab; Physicians' Choice
Intervention description: Ofatumumab IV, initial dose 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks. After 24 weeks of ofatumumab treatment, patients who have achieved at least stable disease or better, and whom the investigator would deem appropriate for the therapy to continue, would undergo a second randomisation (2:1) to either 1) an additional ofatumumab dose regimen of 2000 mg once every 4 weeks for up to an additional 24 weeks, or 2) no further therapy (i.e. observation only).; Non-ofatumumab containing regimen as per physicians' choice for up to 6 months. Permitted therapies include treatments approved for CLL, and well established standards of care for CLL.
Intervention MeSH terms: Ofatumumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: OMB157; Lymphocytic; Chronic; Safety; Refractory; Chronic Lymphocytic Leukemia; Oncology; Ofatumumab; Efficacy; Physicians' Choice; Bulky Fludarabine Refractory Chronic Lymphocytic Leukemia; CLL

Summary:

      The purpose of this study was to confirm the clinical benefit observed in the pivotal
      registration study, Hx-CD20-406. The Committee for Medicinal Products for Human Use (CHMP)
      required that a randomized study be conducted in CLL patients with bulky
      fludarabine-refractory disease as a specific obligation for grant of conditional approval for
      ARZERRA™ in the European Union (EU). This study compared ofatumumab with the physicians'
      choice of therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults with documented diagnosis of active CLL requiring treatment

          -  Bulky lymphadenopathy, defined as at least 1 lymph node >5 cm

          -  Must be refractory to fludarabine treatment

          -  Age 18 yrs or older

          -  At least 2 prior therapies for CLL

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Signed written informed consent

        Exclusion Criteria:

          -  Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant
             within 6 months

          -  Treatment with any unapproved drug substance or experimental therapy within 4 weeks,
             or currently participating in another interventional clinical study

          -  CLL transformation, prolymphocytic leukemia, or central nervous system (CNS)
             involvement of CLL

          -  Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated
             with progressive disease requiring anti-CLL treatment

          -  Chronic or current active infectious disease requiring systemic antibiotics,
             antifungal, or antiviral treatment

          -  Human immunodeficiency virus (HIV) positive

          -  Significant concurrent, uncontrolled medical condition

          -  Other past or current malignancy (with the exception of basal cell carcinoma of the
             skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully
             treated with curative intent at least 2 years prior to trial entry

          -  Non-protocol corticosteroid usage except a maintenance dose corresponding to less than
             or equal to 10 mg prednisone

          -  Abnormal lab values: Creatinine > 2.0 times upper normal limit (unless normal
             creatinine clearance), or total bilirubin > 2.0 times upper normal limit (unless due
             to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase
             (ALT) > 2.5 times upper normal limit (unless due to liver involvement of CLL)

          -  Known or suspected hypersensitivity to ofatumumab

          -  Lactating or pregnant women or female patients of child-bearing potential (or male
             patients with such partners) not willing to use adequate contraception