Ofatumumab-based Induction Chemoimmunotherapy in Previously Untreated Patients With CLL/SLL
Condition: Small Lymphocytic Lymphoma; CLL (Chronic Lymphocytic Leukemia)
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      - Ofatumumab was approved by the U.S. Food and Drug Administration to treat patients with
      chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not responded
      to standard chemotherapy. Ofatumumab is a substance that recognizes specific types of white
      blood cells called B-lymphocytes, which become cancerous in CLL/SLL. Ofatumumab attaches to a
      molecule called CD20, which is found on the surface of B-cells, and destroys them. Previous
      studies have shown that ofatumumab can decrease the number of B-cells in patients with
      CLL/SLL who have been treated with chemotherapy, but more research is needed to determine it
      if can also be used to treat patients with previously untreated CLL/SLL.

      Objectives:

      - To determine a safe and effective dose of ofatumumab, along with chemotherapy, to treat
      chronic lymphocytic leukemia or small lymphocytic lymphoma.

      Eligibility:

      - Individuals at least 18 years of age who have been diagnosed with CLL or SLL that has not
      been treated with chemotherapy.

      Design:

        -  Eligible participants will be screened with a physical exam, blood samples, lymph node
           and bone marrow biopsies, and imaging studies.

        -  Participants will be separated into 2 groups: all participants will receive ofatumumab
           and fludarabine, and some participants will be selected to also receive cyclophosphamide
           (based on results of certain blood tests).

        -  Participants will receive the study drugs (ofatumumab and fludarabine, and optional
           cyclophosphamide) by infusion for a maximum of 6 days, followed by 21 days off drug.

        -  Participants will have 6 cycles of treatment according to a schedule set by the study
           doctors, and may have their dose levels adjusted if side effects develop.

        -  Participants who have disease remaining after 6 cycles will receive additional
           ofatumumab every 2 months, starting 2 months after the end of the 6th cycle and
           continuing for a total of 4 doses, before entering the follow-up phase of the trial.
           Participants who do not have residual disease after 6 cycles will not receive additional
           therapy, and will immediately enter the follow-up phase of the trial.

        -  Participants will have a follow-up exam every 2 to 4 months for 2 years after the end of
           treatment, and then as required by the study doctors for as long as the study remains
           open. These visits will involve a full medical exam, blood samples, lymph node and bone
           marrow biopsies, and imaging studies.
    

Detailed description: 
      OUTLINE:

      Patients with adverse interphase cytogenetics (11q22 or 17p13 deletion) receive FCO induction
      therapy:

        -  Ofatumumab is given IV on day 1 (300 mg) and day 8 (1000 mg) of course 1 and on day 1
           (1000 mg) of all subsequent courses.

        -  Fludarabine phosphate (25mg/m2/d) and cyclophosphamide (250mg/m2/d) are given IV on days
           2 through 4 of course 1 and on days 1 through 3 of all subsequent courses. Patients age
           70 or older will be given reduced doses of fludarabine (20mg/m2/d) and cyclophosphamide
           (150mg/m2/d).

        -  Treatment repeats every 28 days for up to 6 courses in the absence of disease
           progression.

      Patients without adverse interphase cytogenetics receive FO induction therapy:

        -  Ofatumumab is given IV on day 1 (300mg) and day 8 (1000mg) of course 1 and on day 1
           (1000mg) of all subsequent courses.

        -  Fludarabine phosphate (25mg/m2/d) is given IV on days 2 through 6 of course 1 and on
           days 1 through 5 of all subsequent courses.

        -  Treatment repeats every 28 days for up to 6 courses in the absence of disease
           progression.

      All patients are evaluated for minimal residual disease (MRD) by four-color flow cytometric
      analysis of the peripheral blood after completion of FO or FCO induction therapy, and are
      subsequently stratified into two groups:

        -  Patients who are MRD-positive and without evidence of disease progression proceed to
           consolidation therapy beginning approximately 5 months after completion of induction
           therapy, consisting of ofatumumab (1000mg) given IV on day 1 of all courses. Treatment
           repeats every 2 months for up to 4 courses in the absence of disease progression.
           Patients are followed clinically 2 and 6 months after the last dose of ofatumumab is
           given, and then every 6 months thereafter.

        -  Patients who are MRD-negative and without evidence of disease progression are followed
           clinically every 4 months for 1 year and every 6 months thereafter.
    

Intervention name(s): Fludarabine Phosphate; Ofatumumab; Cyclophosphamide
Intervention type(s): Drug; Biological; Drug
Intervention description(s): Given IV; Given IV; Given IV
Other intervention name(s): Fludara; Arzerra; Cytoxan; Neosar
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Ofatumumab
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Arzerra; Chemoimmunotherapy; SLL; Monoclonal Antibody Therapy; CLL; Ofatumumab