Ofatumumab for Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Ofatumumab
Intervention description: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Intervention MeSH terms: Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Ofatumumab

Summary:

      The risk of immunosuppression deters many patients from receiving fludarabine, while
      combination chemotherapy regimens are poorly tolerated by elderly or infirm chronic
      lymphocytic leukemia (CLL) patients. Previous studies by our group and others have shown that
      rituximab is safe and well tolerated when used as a single agent in patients with CLL. In
      addition, maintenance therapy with rituximab was well tolerated by CLL patients, with
      probable prolongation of progression-free survival (Hainsworth et al. 2003). Based on pre
      clinical and clinical studies indicating possible increased efficacy of ofatumumab in
      patients with CLL, we wish to develop an antibody-only regimen for older patients and
      patients who refuse fludarabine-based regimens.
    

Eligibility criteria:

        Inclusion Criteria:

          1. CD20+ B-cell chronic lymphocytic leukemia (B-CLL) or small lymphocytic lymphoma
             according to NCI criteria (see Appendix B).

          2. Previously untreated CLL or small lymphocytic lymphoma (SLL).

          3. Patients must require treatment according to NCI-Working Group guidelines (see
             Appendix C).

          4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (see Appendix
             A).

          5. Laboratory values as follows ≤7 days of initiation of treatment:

               -  Creatinine <3.0 mg/dL

               -  Aspartate amino transferase (AST) or alanine amino transferase (ALT) and alkaline
                  phosphatase (ALP) must be <3 x upper limit of normal (ULN)

               -  Total bilirubin <1.5 x the institutional ULN

          6. Patients must be hepatitis B sAg negative. Note: Patients who are HepB sAg negative
             but are HepB cAb positive (regardless of HepB sAb status) will NOT be allowed.

          7. Women of childbearing potential must have a negative serum pregnancy test performed ≤7
             days prior to start of treatment. Women of childbearing potential or men with partners
             of childbearing potential must use effective birth control measures during treatment.
             If a woman becomes pregnant or suspects she is pregnant while participating in this
             study, she must agree to inform her treating physician immediately.

          8. Patients ≤ 65 years of age, or patients 18-64 years of age who have declined
             fludarabine-based regimens, are eligible.

          9. Patient must be accessible for treatment and follow-up.

         10. Patients must be able to understand the nature of this study, give written informed
             consent prior to study entry, and comply with study requirements.

        Exclusion Criteria:

          1. Previous therapy for CLL/SLL. (Patients who have received steroids or IVIG for
             autoimmune complications of CLL are eligible).

          2. Current active hepatic or biliary disease (with the exception of patients with
             Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver
             disease, per assessment by the treating physician).

          3. Active bacterial or viral infection, or infection requiring intravenous antibiotic
             treatment at the time of accrual.

          4. Central nervous system lymphoma/CLL.

          5. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richters
             transformation).

          6. History of other malignancy within 2 years of study entry which could affect
             compliance with the protocol or interpretation of results. Patients with a history of
             curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma
             of the cervix, low grade, early-stage, localized prostate cancer treated surgically
             with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with
             curative intent, are generally eligible. These cases should be discussed with the
             study chair or study co-chair prior to enrollment.

          7. Patients who are HepB sAg positive and/or HepB cAb positive.

          8. Concurrent severe, intercurrent illness including, but not limited to, ongoing or
             active infection, or psychiatric illness/social situations that would limit compliance
             with study requirements.

          9. Any condition that would prevent patient comprehension of the nature of, and risk
             associated with, the study.

         10. A serious underlying medical condition that would impair the ability of the patient to
             receive protocol treatment.

         11. A major surgical procedure, open biopsy, or significant traumatic injury ≤28 days of
             beginning treatment, or anticipation of the need for major surgery during the course
             of the study.

         12. Treatment with any known non-marketed drug substance or experimental therapy within 5
             terminal half lives or 4 weeks prior to visit 1, whichever is longer. Patients may not
             receive any other investigational or anti-cancer treatments while participating in
             this study.