Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: Chronic Lymphocytic Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Cyclophosphamide; Laboratory Biomarker Analysis; Ofatumumab; Pentostatin
Intervention description: Given IV; Correlative studies; Given IV; Given IV
Intervention MeSH terms: Vidarabine; Cyclophosphamide; Ofatumumab; Pentostatin; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 82.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving ofatumumab together with pentostatin and
      cyclophosphamide works in treating patients with untreated chronic lymphocytic leukemia or
      small lymphocytic lymphoma. Monoclonal antibodies, such as ofatumumab, can block the ability
      of cancer cells to grow and spread. Drugs used in chemotherapy, such as pentostatin and
      cyclophosphamide, work in different ways to stop the growth of cancer cells, either by
      killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving
      ofatumumab together with pentostatin and cyclophosphamide may be a better way to block cancer
      growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of CLL according to the National Cancer Institute (NCI) criteria or SLL
             according to the World Health Organization (WHO) criteria, including previous
             documentation of:

          -  Biopsy-proven SLL

          -  Diagnosis of CLL according to NCI working group criteria as evidenced by all of the
             following:

               -  Peripheral blood lymphocyte count of > 5,000/mm^3 consisting of small to moderate
                  size lymphocytes, with < 55% prolymphocytes

               -  Immunophenotyping consistent with CLL defined as:

                    -  The predominant population of lymphocytes share both B-cell antigens (CD19,
                       CD20 [typically dim expression], or CD23) as well as CD5 in the absence of
                       other pan-T-cell markers (CD3, CD2, etc.)

                    -  Clonality as evidenced by kappa or lambda light chain expression (typically
                       dim immunoglobulin expression)

                    -  Note: splenomegaly, hepatomegaly, or lymphadenopathy are not required for
                       the diagnosis of CLL

               -  Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by
                  demonstrating a negative FISH analysis for t(11;14)(immunoglobulin heavy
                  [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy or negative
                  immunohistochemical stains for CCND1 on involved tissue biopsy

          -  Patients must be previously untreated and meet at least one of the following
             indications for chemotherapy:

               -  Evidence of progressive marrow failure as manifested by the development of or
                  worsening anemia (=< 11 g/dl) and/or thrombocytopenia (=< 100,000/mm^3) not due
                  to autoimmune disease

               -  Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly

               -  One or more of the following disease-related symptoms:

                    -  Weight loss > 10% within the previous 6 months

                    -  Extreme fatigue attributed to CLL

                    -  Fevers > 100.5 degree Fahrenheit for 2 weeks without evidence of infection

                    -  Drenching night sweats without evidence of infection

               -  Progressive lymphocytosis due to CLL with an increase of > 50% over a two-month
                  period or an anticipated doubling time of less than six months

                    -  Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL
                       will be considered prior therapy; nutraceutical treatments with no
                       established benefit in CLL (such as epigallocatechin gallate [EGCG], found
                       in green tea or other herbal treatments) will not be considered "prior
                       treatment"

                    -  Marked hypogammaglobulinemia or the development of a monoclonal protein in
                       the absence of any of the above criteria for active disease are not
                       sufficient for protocol therapy

          -  Serum creatinine =< 1.5 x upper normal levels (UNL)

          -  Total bilirubin =< 1.5 x UNL unless due to Gilbert's disease; if total bilirubin is >
             1.5 x UNL, a direct bilirubin should be performed and must be < 1.5 mg/dL for
             Gilbert's to be diagnosed

          -  Aspartate aminotransferase (AST) =< 3.0 x UNL and alanine aminotransferase (ALT) =<
             3.0 x UNL (unless due to hemolysis or CLL)

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0, 1, or 2

          -  Willingness to provide blood samples as required

          -  Able to adhere to the study visit schedule and other protocol requirements

        Exclusion Criteria:

          -  Any of the following comorbid conditions:

               -  New York Heart Association Class III or IV heart disease

               -  Recent myocardial infarction (< 1 month)

               -  Uncontrolled infection

               -  Infection with the human immunodeficiency virus (HIV/acquired immunodeficiency
                  syndrome [AIDS])

               -  Infection with known chronic, active Hepatitis C

               -  Positive serology for hepatitis B (HB) defined as a positive test for HB surface
                  antigen (HBsAg); in addition, if negative for HBsAg but HB core antibody (HBcAb)
                  positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will
                  be performed and if positive the subject will be excluded

          -  Pregnant women

          -  Nursing women

          -  Men or women of childbearing potential who are unwilling to employ adequate
             contraception

          -  Other active primary malignancy requiring treatment or limiting survival to =< 2 years

          -  Any radiation therapy =< 4 weeks prior to registration

          -  Any major surgery =< 4 weeks prior to registration

          -  Current use of corticosteroids; EXCEPTION: low doses of steroids (< 10 mg of
             prednisone or equivalent dose of other steroid) used for treatment of non-hematologic
             medical conditions; Note: previous use of corticosteroids is allowed

          -  Active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic
             treatment; patients who have a positive Coombs test but no evidence of hemolysis are
             NOT excluded from participation