Pentostatin, Cyclophosphamide, and Rituximab Followed By Campath-1H in Patients With Relapsed or Refractory B-Cell CLL
Condition: Leukemia
MeSH terms: Leukemia
Intervention: rituximab; cyclophosphamide; pentostatin; Alemtuzumab
Intervention MeSH terms: Cyclophosphamide; Rituximab; Alemtuzumab; Pentostatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: refractory chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia

Summary:

      RATIONALE: Drugs used in chemotherapy, such as pentostatin, cyclophosphamide, and CAMPATH-1H
      work in different ways to stop cancer cells from dividing so they stop growing or die.
      Monoclonal antibodies, such as rituximab can locate cancer cells and either kill them or
      deliver cancer-killing substances to them without harming normal cells. Combining
      chemotherapy with monoclonal antibody therapy may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well pentostatin, cyclophosphamide, rituximab,
      and CAMPATH-1H work in treating patients with relapsed or refractory B-cell chronic
      lymphocytic leukemia.
    

Eligibility criteria:

        Inclusion criteria:

          -  Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria:

               -  Peripheral blood absolute lymphocyte count greater than 5,000/mm^3

               -  Lymphocytosis must comprise small to moderate size lymphocytes with no greater
                  than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically

               -  Phenotypically characterized CLL defined by the following:

                    -  Predominant population of cells share B-cell antigens with CD5 in the
                       absence of other pan-T-cell markers (CD3 or CD2)

                    -  B cell expresses either kappa or lambda light chains

                    -  Surface immunoglobulin with low cell surface density expression

          -  Requires chemotherapy, as indicated by any of the following:

               -  Disease-related symptoms

                    -  Weight loss of 10% or more within the past 6 months

                    -  Extreme fatigue

                    -  Fevers greater than 100.5°F for 2 weeks without evidence of infection

                    -  Night sweats without evidence of infection

               -  Evidence of progressive marrow failure manifested by the development of or
                  worsening anemia (hemoglobin no greater than 10 g/dL) and/or thrombocytopenia
                  (platelet count no greater than 100,000/mm^3)

               -  Massive (i.e., greater than 6 cm below left costal margin) or progressive
                  splenomegaly

               -  Massive nodes or clusters (i.e., greater than 10 cm in longest diameter) or
                  progressive adenopathy

               -  Progressive lymphocytosis with an increase of greater than 50% over a 2-month
                  period OR an anticipated doubling time of less than 6 months

          -  Demonstrated progression after at least 1 course of either an alkylating agent-based
             or purine nucleoside-based (e.g., fludarabine) regimen OR failed to achieve a
             meaningful response OR relapsed after prior therapy

               -  Patients who have relapsed after a pentostatin-based regimen are eligible
                  provided the response was greater than 12 months prior to study entry

          -  18 and over

          -  ECOG Performance Status 0-2

          -  Bilirubin no greater than 2 mg/dL (unless secondary to tumor, hemolysis, or Gilbert
             syndrome)

          -  Creatinine no greater than 2.0 mg/dL

          -  Creatinine clearance ≥ 30 mL/min

          -  Negative pregnancy test

          -  Fertile patients must use 2 methods of effective contraception (including 1 barrier
             method) for at least 28 days before starting lenalidomide, while participating in the
             study, and for at least 28 days after discontinuation/stopping lenalidomide

          -  At least 8 weeks since prior rituximab

          -  At least 6 weeks since prior chemotherapy

          -  At least 1 year since prior pentostatin, cyclophosphamide, and rituximab (PCR) therapy

               -  PCR therapy at least 1 year prior to study entry allowed

        Exclusion criteria:

          -  Bone marrow dysplasia related to prior therapy

          -  New York Heart Association class III or IV heart failure

          -  Prior lenalidomide

          -  Other malignancy within the past 2 years except squamous cell or basal cell skin
             cancer or carcinoma in situ of the cervix

          -  Pregnant or nursing

          -  Concurrent oral or IV antibiotics for active infection