RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells are rejected by the body's tissues. Mycophenolate mofetil, cyclosporine, and donor white blood cells may prevent this rejection.

PURPOSE: Phase I/II trial to study the effectiveness of donor peripheral stem cell transplantation in treating patients who have acute lymphoblastic leukemia.

Condition	Treatment or Intervention	Phase
adult acute lymphoblastic leukemia in remission childhood acute lymphoblastic leukemia in remission	Drug: allogeneic lymphocytes  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: graft versus tumor induction  Procedure: leukocyte therapy  Procedure: peripheral blood lymphocyte therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase I Phase II

OBJECTIVES: Primary

• Determine the 1-year disease-free survival of patients with acute lymphoblastic leukemia in complete remission treated with nonmyeloablative allogeneic peripheral blood stem cell transplantation from HLA-matched unrelated donors.

Secondary

• Determine the day 200 transplant-related mortality in patients treated with this regimen.
• Determine the efficacy of donor lymphocyte infusions (DLI) in patients treated with this regimen.
• Determine the toxicity of DLI in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV on days -4 to -2. Patients undergo total body irradiation on day 0 followed by allogeneic peripheral blood stem cell infusion. Patients also receive oral cyclosporine twice daily on days -3 to 100 with a taper from day 101-177 and oral mycophenolate mofetil 3 times daily on days 0-40 with a taper from day 41-96.

Beginning 1-2 weeks after withdrawal of immunosuppression, patients with no evidence of acute graft-vs-host disease grade 2 or greater and no morphological disease progression may receive up to 3 donor lymphocyte infusions (DLI) IV over 30 minutes.

Patients are followed monthly for 4 months, at 6, 12, 18, and 24 months, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 30 patients (20 adults and 10 children) will be accrued for this study within 2 years.

Ages Eligible for Study:  up to  75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of adult or pediatric acute lymphoblastic leukemia (ALL)
• Age 50 to 75 with high-risk disease in complete remission (CR)1 OR disease in CR2 or greater
• Age 18 to 49 with high-risk disease in CR1 OR disese in CR2 or greater and ineligible for or refused conventional allogeneic transplantation
• CR is defined as:
• Less than 5% blasts by morphology on a bone marrow biopsy and absence of peripheral blasts
• High-risk adult ALL in CR1 defined as 1 or more of the following:
• 30 years of age or over
• Non T-cell phenotype
• Cytogenetic abnormalities (e.g., t(9;22), t(4;11), trisomy 8, or monosomy 7)
• Failure to achieve CR after 4 weeks of induction chemotherapy
• Under 18 years of age with high-risk disease in CR1 OR disease in CR2 or greater and ineligible for conventional allogeneic transplantation
• High-risk pediatric ALL in CR1 defined as 1 or more of the following:
• Cytogenic abnormalities (e.g., t(9;22) with WBC ≥ 25,000/mm3 at diagnosis, t(4;11) if under 1 year of age or 10 years of age and over, hypodiploidy [< 45 chromosomes])
• Failure to achieve CR after 4 weeks of induction chemotherapy
• Persistent peripheral blasts after 1 week of induction chemotherapy
• No active CNS disease
• Must have unrelated donor matched for HLA-DRB1, and -DQB1 by high-resolution typing
• Single allele disparity allowed for HLA-A, -B, or -C

PATIENT CHARACTERISTICS: Age:

• See Disease Characteristics
• 75 and under

Performance status:

• Karnofsky 50-100% (17 years of age and over)
• Lansky 40-100% (under 17 years of age)

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• No fulminant liver failure
• No alcoholic hepatitis
• No hepatic encephalopathy ≥ grade 2
• No hepatic synthetic dysfunction
• No prolongation of PT
• INR < 2.5
• No intractable ascites related to portal hypertension
• No bacterial or fungal liver abscess
• No chronic viral hepatitis or biliary obstruction AND bilirubin ≤ 5 mg/dL
• No symptomatic biliary disease

Renal:

• Not specified

Cardiovascular:

• Cardiac ejection fraction ≥ 35%

Pulmonary:

• No requirement for supplementary continuous oxygen OR
• DLCO ≥ 40% of predicted

Other:

• HIV negative
• No history of bleeding esophageal varices
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting

Study chairs or principal investigators

George Georges, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000069212; FHCRC-1623.00; NCI-H02-0085
Record last reviewed:  July 2004
Record first received:  March 8, 2002
ClinicalTrials.gov Identifier:  NCT00031655
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-17