Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: alemtuzumab; rituximab; pentostatin; sargramostim
Intervention MeSH terms: Rituximab; Alemtuzumab; Pentostatin; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: refractory chronic lymphocytic leukemia; recurrent small lymphocytic lymphoma; B-cell chronic lymphocytic leukemia

Summary:

      RATIONALE: Drugs used in chemotherapy, such as pentostatin, work in different ways to stop
      the growth of cancer cells, either by killing the cells or by stopping them from dividing.
      Monoclonal antibodies, such as alemtuzumab and rituximab, can block cancer growth in
      different ways. Some block the ability of cancer cells to grow and spread. Others find cancer
      cells and help kill them or carry cancer-killing substances to them. Giving pentostatin
      together with alemtuzumab and rituximab may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving pentostatin together with
      alemtuzumab and rituximab works in treating patients with relapsed or refractory chronic
      lymphocytic leukemia or small lymphocytic lymphoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) or small
             lymphocytic lymphoma (SLL) meeting the following criteria:

               -  Minimum threshold peripheral blood lymphocyte count of 5 x 10^9/L (CLL variant)
                  OR adenopathy > 1 cm or palpable splenomegaly (SLL variant)

               -  Immunophenotypic demonstrations of a population of B lymphocytes (as defined by
                  CD19+) that are monoclonal (by light chain exclusion) AND have ≥ 3 of the
                  following characteristics:

                    -  CD5+

                    -  CD23+

                    -  Dim surface light chain expression

                    -  Dim surface CD20 expression

                    -  FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative
                       for cyclin D1 expression

          -  Must have progressive disease as indicated by any of the following characteristics
             (based on standard criteria for treatment):

               -  Symptomatic CLL characterized by any of the following:

                    -  Weight loss > 10% within the past 6 months

                    -  Extreme fatigue

                    -  Fevers > 38.5° C (not due to infection)

                    -  Drenching night sweats without evidence of infection

               -  Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet
                  count < 100 x 10^9/L

               -  Massive and progressive splenomegaly (> 6 cm below left costal margin)

               -  Massive (> 10 cm) or rapidly progressive lymphadenopathy

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-3

          -  Creatinine ≤ 2 times upper limit of normal (ULN)

          -  Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 times ULN

          -  AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)

          -  Willing to provide mandatory blood samples for research studies

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for up to 12 months after
             completion of study treatment

          -  No other active primary malignancy that requires treatment or limits survival to ≤ 2
             years

          -  No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell
             aplasia

          -  No New York Heart Association class III or IV heart disease

          -  No myocardial infarction within the past month

          -  No uncontrolled infection

          -  No HIV infection or AIDS

          -  No active hepatitis B infection (i.e., HBsAg or HBeAg positivity) or hepatitis C
             infection by serology

          -  No other comorbid condition

        PRIOR CONCURRENT THERAPY:

          -  No more than 3 prior treatment regimens for CLL that included purine analogue drugs
             (e.g., fludarabine, pentostatin, or cladribine) OR previously untreated CLL in
             patients with high-risk disease due to 17p13 deletion on FISH analysis

          -  More than 4 weeks since prior major surgery

          -  More than 2 months since prior alemtuzumab

          -  Prior corticosteroids allowed

          -  No concurrent continuous systemic corticosteroids