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
Intervention: Fludarabine Phosphate; Ofatumumab; Cyclophosphamide
Intervention description: Given IV; Given IV; Given IV
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Arzerra; Chemoimmunotherapy; SLL; Monoclonal Antibody Therapy; CLL; Ofatumumab

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Histologically confirmed CLL or SLL as defined by the following:

          -  B-lymphocytosis greater than 5000 cells/micro L (may be less than 5000 cells/micro L
             if lymphadenopathy is present with histologic confirmation of lymph node involvement
             by SLL).

          -  Immunophenotypic profile consistent with CLL as demonstrated by flow cytometry

          -  Appropriate immunophonotype (CD5/19/23+)

          -  Clonality of lymphocytosis confirmed by flow cytometry

          -  large lymphocytes less than 55 % of blood lymphocytes

        Active disease as defined by at least one of the following:

          -  Weight loss greater than or equal to10 percent within the previous 6 months

          -  Extreme fatigue

          -  Fevers of greater than 100.5 degree F for greater than or equal to 2 weeks without
             evidence of infection

          -  Night sweats for more than one month without evidence of infection

          -  Evidence of progressive marrow failure as manifested by the development of, or
             worsening of, anemia and/or thrombocytopenia

          -  Massive or progressive splenomegaly

          -  Massive nodes or clusters or progressive lymphadenopathy

          -  Progressive lymphocytosis with an increase of greater than 50% over a 2 month period,
             or an anticipated doubling time of less than 6 months 0

        Measurable disease (defined as two dimensional disease on imaging or quantifiable leukemic
        disease).

        Ages 18 and over.

        EXCLUSION CRITERIA:

        Prior monoclonal antibody therapy with agents having anti-CLL activity

        Prior cytotoxic chemotherapy with agents having anti-CLL activity (Fludarabine,
        Cyclophosphamide, Bendamustine, Chlorambucil)

        Transformed CLL

        Active autoimmune hemolytic anemia or thrombocytopenia

        Any medical condition that requires the chronic use of corticosteroids

        Active or latent Hepatitis B infection

        HIV infection

        Severe chronic obstructive pulmonary disease, severe cardiac disease, or other uncontrolled
        medical condition that would, in the opinion of the principal investigator, place the
        subject at an unreasonable risk of life-threatening adverse events due to
        chemoimmunotherapy

        ECOG performance status 3 or worse

        Creatinine greater than or equal to 2 mg/dL or creatinine clearance less than or equal to
        30 mL/min

        Bilirubin greater than or equal to 2 mg/dL or active hepatic or biliary disease (with
        exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic
        liver disease per investigator assessment)

        Female patients: Current pregnancy or unwilling to take oral contraceptives or refrain from
        pregnancy if of childbearing potential or currently breastfeeding. Male patients who are
        unwilling to follow the contraception requirements described in this protocol.

        Psychiatric illness/social situations that would limit the patient s ability to tolerate
        and/or comply with study requirements.

        Unable to understand the investigational nature of the study or give informed consent.