RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy and radiation therapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of high-dose combination chemotherapy followed by total-body irradiation and peripheral stem cell transplantation in treating patients with chronic lymphocytic leukemia.

Condition	Treatment or Intervention	Phase
stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia refractory chronic lymphocytic leukemia B-cell Chronic Lymphocytic Leukemia	Drug: cyclophosphamide  Drug: dexamethasone  Drug: etoposide  Drug: filgrastim	Phase I

Further Study Details: 

OBJECTIVES: I. Evaluate engraftment after autografting with CD34 selected peripheral blood stem cells (PBSC) in patients with chronic lymphocytic leukemia (CLL). II. Evaluate the efficacy of CD34 selection for purging CLL from PBSC collection. III. Determine the effectiveness of mobilization chemotherapy with cyclophosphamide, etoposide, and dexamethasone plus filgrastim (granulocyte colony-stimulating factor) to mobilize PBSC in these patients. IV. Describe toxicity and disease response to a conditioning regimen of total body irradiation and cyclophosphamide in these patients.

PROTOCOL OUTLINE: There are 3 phases to the treatment plan: Cytoreductive chemotherapy can be given by conventional chemotherapy. Patients are treated until at least a good partial remission. Patients will have CD34 selected peripheral blood stem cells (PBSC) stored after treatment with mobilization chemotherapy followed by filgrastim (granulocyte colony-stimulating factor; G-CSF). Cyclosphosphamide (CTX) IV is given over 1 hour. Etoposide (VP-16) is given over 1-2 hours on day 2. Dexamethasone is given 4 times a day on days 1-3. G-CSF is given subcutaneously daily beginning 2 days after chemotherapy and continuing until PBSC collection is completed. At least 4 weeks should ensue after mobilization chemotherapy before proceeding with the transplant. Patients are treated with TBI on days -6, -5, and -4 and CTX on days -3 and -2. PBSC are infused on day 0.

PROJECTED ACCRUAL: A total of 15 patients will be entered in this study.

Ages Eligible for Study:  17 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnostically proven intermediate, advanced, or high risk chronic lymphocytic leukemia of the B cells with marrow tumor reduced by prior therapy
• Marrow tumor content no greater than 30% of total nucleated cells
• Patients age 50 and under who have high risk disease are eligible
• Patients age 65 and under who have intermediate or high risk disease that has failed at least 1 therapy including an alkylating agent or fludarabine are eligible
• No history of transformation to aggressive lymphoma (Richter's syndrome)

--Prior/Concurrent Therapy--

• See Disease Characteristics No prior radiation therapy to chest or abdomen greater than 2,000 Gy

--Patient Characteristics--

• Age: 17 to 65
• Performance status: Karnofsky 70%-100%
• Life expectancy: Not severely limited by illness other than leukemia
• Hematopoietic: Absolute neutrophil count greater than 2,000/mm3 (no growth factor support); Platelet count greater than 120,000/mm3 (unless documented active autoimmune thrombocytopenia); Hemoglobin greater than 10 g/dL (unless documented active autoimmune anemia) No coexisting myelodysplasia
• Hepatic: Bilirubin no greater than 2.0 mg/dL
• Renal: Creatinine clearance at least 50 mL/min
• Cardiovascular: No cardiac disease that would limit ability to receive cytoreductive therapy and compromise survival
• Pulmonary: No pulmonary disease that would limit ability to receive cytoreductive therapy and compromise survival
• Other: No HIV antibody; Not pregnant

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

David G. Maloney,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000064852; FHCRC-962.00; NCI-H96-0925
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00002788
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08