RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving fludarabine together with radiation therapy before transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine together with radiation therapy works in treating patients who are undergoing donor stem cell transplant for chronic lymphocytic leukemia or small lymphocytic lymphoma that did not respond to fludarabine.

Condition	Treatment or Intervention	Phase
refractory chronic lymphocytic leukemia recurrent small lymphocytic lymphoma B-cell Chronic Lymphocytic Leukemia T-cell chronic lymphocytic leukemia Prolymphocytic Leukemia	Drug: cyclosporine  Drug: fludarabine  Drug: mycophenolate mofetil  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare 18-month survival of patients with fludarabine-refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with nonmyeloablative conditioning comprising fludarabine and low-dose total-body irradiation followed by allogeneic hematopoietic stem cell transplantation with that of historical controls treated with alemtuzumab.

Secondary

• Determine the overall response rate (complete response and partial response) by standard morphologic, flow cytometric, and molecular techniques in patients treated with this regimen.
• Determine the rate of relapse or disease progression in patients treated with this regimen.
• Determine the incidence of regimen-related toxicity and infections within the first 200 days after transplantation in patients treated with this regimen.
• Determine the incidence of transplant-related mortality within the first year after transplantation in patients treated with this regimen.
• Determine the incidence of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD in patients treated with this regimen.
• Determine the graft vs leukemia effect in terms of the mechanism of resistance in relapsed or non-responding patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Conditioning regimen: Patients receive fludarabine IV on days -4 to -2. Patients undergo single fraction low-dose total-body irradiation (TBI) on day 0.
• Allogeneic stem cell transplantation: After completion of TBI, patients undergo allogeneic hematopoietic stem cell transplantation on day 0.
• Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 100 followed by a taper to day 177. Patients also receive oral mycophenolate mofetil 3 times daily on days 0-40 followed by a taper to day 96 . After completion of study treatment, patients are followed at 6 months, 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 1 year.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma, as defined by all of the following criteria:
• Absolute peripheral lymphocyte count (mature-appearing lymphocytes) > 5,000/mm^3 that has persisted for ≥ 4 weeks
• Mature lymphocytes with < 55% cells comprising atypical lymphocytes, prolymphocytes, or lymphoblasts in peripheral blood
• Normal or hypercellular bone marrow aspirate and biopsy with ≥ 30% of nucleated cells of lymphoid origin
• At least 1 B-cell marker (CD19, CD20, or CD23) AND CD5 in peripheral blood or bone marrow by flow cytometry
• T-cell CLL OR CLL that has progressed to prolymphocytic leukemia allowed
• Fludarabine-refractory disease, as defined by 1 of the following criteria:
• Failed to meet NCI Working Group criteria for complete or partial response after therapy with regimens containing fludarabine (or another nucleoside analog [e.g., cladribine or pentostatin])
• Disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
• Suitable unrelated donor available
• Matched for HLA-A, -B, -C, -DRB1, and -DQB1 by high resolution typing
• Only a single allele disparity for HLA-A, -B, or -C by high resolution typing allowed
• No marrow donor
• No HLA-matched related donor
• No active CNS involvement with CLL

PATIENT CHARACTERISTICS: Age

• Any age

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• No fulminant liver failure
• No cirrhosis of the liver with evidence of portal hypertension
• No hepatic damage with bridging fibrosis
• No alcoholic hepatitis
• No esophageal varices
• No history of bleeding esophageal varices
• No hepatic encephalopathy
• No uncorrectable hepatic synthetic dysfuntion as evidenced by prolongation of PT
• No ascites related to portal hypertension
• No bacterial or fungal liver abscess
• No chronic viral hepatitis with bilirubin > 3 mg/dL
• No biliary obstruction
• No symptomatic biliary disease

Renal

• Not specified

Cardiovascular

• Ejection fraction ≥ 40% by MUGA or echocardiogram

Pulmonary

• DLCO ≥ 40%
• Pulmonary nodules allowed at the discretion of the principal investigator
• No requirement for continuous supplementary oxygen
• No severe deficits in pulmonary function as determined by pulmonary consultant

Immunologic

• HIV negative
• HTLV-1 and HTLV-2 negative

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception before, during, and for 12 months after transplantation
• No solid tumor or melanoma > stage I within the past 5 years
• No other concurrent malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Chemotherapy

Chemotherapy

• See Disease Characteristics
• More than 3 weeks since prior intensive systemic chemotherapy* for cytoreduction NOTE: *Cytokine therapy, low-dose cytarabine, chlorambucil, and rituximab are not considered systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy to high-risk sites of bulky disease or skeletal lesions allowed for cytoreduction

Surgery

• Not specified

Other

• More than 2 weeks since other prior cytotoxic agents for cytoreduction
• No other concurrent anticancer therapy

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5623,  United States; Recruiting
Colorado
      Rocky Mountain Cancer Centers - Denver Midtown, Denver,  Colorado,  80218,  United States; Recruiting
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Texas
      Charles A. Sammons Cancer Center, Dallas,  Texas,  75246,  United States; Recruiting
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting
Germany
      Medizinische Universitaetsklinik I, Cologne,  D-50924,  Germany; Recruiting
      Universitaet Leipzig, Leipzig,  D-04103,  Germany; Recruiting
Italy
      Universita di Torino, Turin,  10126,  Italy; Recruiting

Study chairs or principal investigators

Michael B. Maris, MD,  Principal Investigator,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000415556; FHCRC-1840.00; NCT00104858
Record last reviewed:  February 2005
Last Updated:  March 15, 2005
Record first received:  March 3, 2005
ClinicalTrials.gov Identifier:  NCT00104858
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08