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 tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Immunosuppressive drugs such as mycophenolate mofetil and cyclosporine may be an effective treatment to prevent rejection. PURPOSE: Phase I/II trial to study the effectiveness of combining chemotherapy, radiation therapy, and peripheral stem cell transplantation followed by immunosuppressive therapy in treating patients who have cancer.

Condition	Treatment or Intervention	Phase
Leukemia Renal Cell Cancer Testicular Cancer ovarian epithelial cancer Lymphoma Breast Cancer Multiple Myeloma kidney tumor	Drug: allogeneic lymphocytes  Drug: cyclosporine  Drug: fludarabine  Drug: mycophenolate mofetil	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the risk of graft rejection associated with the addition of fludarabine to a nonmyeloablative conditioning regimen in patients with malignancies treatable by allogeneic bone marrow (stem cell) transplantation. II. Compare the rate of graft rejection in patients treated with this regimen vs patients previously untreated with fludarabine. III. Determine the rate of acute grade II/IV graft versus host disease (GVHD) and chronic GVHD in these patients treated with fludarabine, low dose total body irradiation, and allogeneic peripheral blood stem cell transplantation followed by immunosuppression with cyclosporine and mycophenolate mofetil.

PROTOCOL OUTLINE: This is a multicenter study. Patients receive fludarabine IV on days -4 to -2, and total body irradiation followed by filgrastim (G-CSF) mobilized allogeneic peripheral blood stem cell transplantation on day 0. Patients also receive oral cyclosporine twice daily on days -3 to 56 and oral mycophenolate mofetil twice daily on days 0 to 27. Following completion of immunosuppression therapy patients with stable mixed chimerism and no evidence of graft versus host disease (GVHD) receive donor lymphocytes IV over 30 minutes on or after day 65. Treatment repeats every 65 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed weekly until day 90 after last lymphocyte infusion, at 4, 6, 12, 18, and 24 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  up to  74 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• 50 to 74 years old and diagnosed with non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or multiple myeloma; Not eligible for curative autologous transplantation or failed prior autologous transplantation; NHL and CLL patients must have failed prior therapy with an alkylating agent and/or fludarabine or be at high risk for relapse; Multiple myeloma patients must have stage II or III disease and received prior chemotherapy OR Under 50 years old and diagnosed with NHL, CLL, or multiple myeloma; Not eligible for curative autologous transplantation; At high risk for regimen related toxicity due to prior autologous transplantation or preexisting medical condition OR Under 75 years old and diagnosed with other malignant disease treatable by allogeneic bone marrow transplantation; Not eligible for curative autologous transplantation; At high risk for toxicity related to standard high dose regimens due to a preexisting chronic disease affecting kidneys, liver, lungs, and heart; Includes the following likely diseases: Myelodysplastic syndrome; Myeloproliferative syndromes; Acute leukemia with less than 10% blasts; Amyloidosis; Hodgkin's disease; Renal cell carcinoma OR Other malignancies for which patient has declined standard allografts
• No rapidly progressive aggressive NHL unless in minimal disease state
• No active CNS involvement
• Must have HLA genotypically or phenotypically identical related donor meeting these criteria: 12 to 74 years old (pediatric donors will provide bone marrow); No identical twin Not pregnant; HIV negative; No known allergy to filgrastim (G-CSF); No concurrent serious systemic illness
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics; No concurrent posttransplantation colony stimulating factors during mycophenolate mofetil
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: Under 75
• Menopausal status: Not specified
• Performance status: Karnofsky 50-100%
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN); SGPT and SGOT under 4 times ULN
• Renal: Renal failure allowed
• Cardiovascular: Cardiac ejection fraction at least 40%; No poorly controlled hypertension
• Pulmonary: No severe defects in pulmonary function; No supplementary continuous oxygen
• Other: Not pregnant or nursing; Fertile patients must use effective contraception during and for 1 year following study; HIV negative

California
      Beckman Research Institute, City of Hope, Los Angeles,  California,  91010,  United States
      Stanford University, Stanford,  California,  94305,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80262,  United States
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States
Germany
      Universitaet Leipzig - Chirurgische Klinik und Poliklinik I, Leipzig,  D-04103,  Germany
Italy
      University of Torino, Torino,  10126,  Italy

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000068184; FHCRC-1533.00; NCI-H00-0062
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  September 11, 2000
ClinicalTrials.gov Identifier:  NCT00006251
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08