Combination Chemotherapy, Total-Body Irradiation, and Alemtuzumab in Treating Patients Undergoing an Autologous Stem Cell Transplant for Stage I, Stage II, Stage III, or Stage IV Chronic Lymphocytic Leukemia
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving combination chemotherapy before a peripheral blood stem cell transplant
      stops the growth of cancer cells by stopping them from dividing or killing them. Giving
      colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells
      move from the bone marrow to the blood so they can be collected and stored. A monoclonal
      antibody, such as alemtuzumab, is given to kill any remaining cancer cells. Chemotherapy and
      radiation therapy (total-body irradiation) are given to prepare the bone marrow for the stem
      cell transplant. The stem cells are then returned to the patient to replace the blood-forming
      cells that were destroyed by the chemotherapy and radiation therapy. Giving combination
      chemotherapy, total-body irradiation, and alemtuzumab together with autologous peripheral
      stem cell transplant may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving combination chemotherapy together
      with total-body irradiation and alemtuzumab works in treating patients undergoing an
      autologous stem cell transplant for stage I, stage II, stage III, or stage IV chronic
      lymphocytic leukemia.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety and feasibility of cytoreductive fludarabine and cyclophosphamide
           followed by high-dose myeloablative therapy comprising total-body irradiation,
           cyclophosphamide, and alemtuzumab in patients undergoing autologous filgrastim
           (G-CSF)-mobilized peripheral blood stem cell transplantation for stage I-IV chronic
           lymphocytic leukemia.

      Secondary

        -  Determine the clinical and molecular remission rate and duration in patients treated
           with this regimen.

        -  Determine the overall survival of patients treated with this regimen.

      OUTLINE: This is a multicenter, open label, nonrandomized study. Patients are assigned to 1
      of 2 cohorts according to time of enrollment.

        -  Cytoreductive induction therapy: All patients receive fludarabine IV and
           cyclophosphamide IV on days 1-3. Treatment repeats every 28 days for 2-4 courses in the
           absence of disease progression or unacceptable toxicity. Patients achieving complete
           response (CR) or partial response (PR) proceed to stem cell mobilization. Patients with
           stage III or IV disease at this point are removed from study.

        -  Stem cell mobilization: All patients receive Dexa-BEAM comprising oral dexamethasone
           once daily on days 1-10; carmustine IV and melphalan IV on day 2; and cytarabine IV
           twice daily and etoposide IV once daily on days 4-7. Patients also receive filgrastim
           (G-CSF) subcutaneously beginning on day 8 and continuing until leukapheresis is
           completed. Patients undergo peripheral blood stem cell (PBSC) harvest between days 20
           and 28. Patients without an adequate number of collected PBSCs may receive a second
           course of Dexa-BEAM. Patients achieving CR or very good PR proceed to high-dose
           myeloablative therapy and PBSC transplantation (PBSCT) with or without consolidation
           therapy.

        -  Consolidation therapy: Beginning between 1-2 months after completion of Dexa-BEAM,
           patients in cohort 2 receive alemtuzumab IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15,
           17, 19, 22, 24, and 26 and then proceed to high-dose myeloablative therapy and PBSCT
           within 1 month after completion of consolidation therapy. Patients in cohort 1 do not
           receive consolidation therapy and proceed directly to high-dose therapy within 3 months
           after completion of stem cell mobilization.

        -  High-dose myeloablative therapy and PBSCT: Patients undergo total-body irradiation on
           days -7 to -5. Patients then receive cyclophosphamide IV on days -4 and -3 and
           alemtuzumab IV over 2 hours on days -10, -9, -8, -6, and -4. Patients undergo PBSCT on
           day 0.

      After completion of study treatment, patients are followed periodically.

      PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
    

Intervention name(s): alemtuzumab; filgrastim; carmustine; cyclophosphamide; cytarabine; dexamethasone; etoposide; fludarabine phosphate; melphalan; autologous bone marrow transplantation; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Cytarabine; Dexamethasone; Cyclophosphamide; Melphalan; Carmustine; Fludarabine; Fludarabine phosphate; Etoposide; Alemtuzumab
Allocation: Non-Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage 0 chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia