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 with donor peripheral stem cells and donor white blood cells may kill more hematologic cancer cells. PURPOSE: Phase I trial to study the effectiveness of fludarabine, total-body irradiation, donor peripheral stem cell transplantation, and donor white blood cell infusions in treating patients who have hematologic cancer.

Condition	Treatment or Intervention	Phase
Leukemia Renal Cell Cancer Lymphoma Eye Cancer Kidney Cancer	Drug: fludarabine	Phase I

Further Study Details: 

OBJECTIVES: I. Determine whether stable allogeneic stem cell engraftment from unrelated donors can be safely established using a nonmyeloablative conditioning regimen comprising fludarabine and total body irradiation in patients with hematologic malignancies or renal cell carcinoma. II. Determine whether donor lymphocyte infusions can be safely used in patients with mixed or full donor chimerism to eliminate persistent or progressive disease. III. Determine the response rate, disease-free survival, disease relapse, and disease-related mortality in these patients treated with this regimen.

PROTOCOL OUTLINE: This is a multicenter study. Cytoreduction: Patients with advanced malignancies may receive cytoreduction and/or radiotherapy at the discretion of the attending physician and protocol chairperson. Conditioning: Patients receive fludarabine IV on days -4 to -2. Patients undergo low-dose total body irradiation followed by infusion of allogeneic peripheral blood stem cells (PBSC) or bone marrow on day 0. Donor lymphocyte infusions: Donor lymphocytes are collected from the PBSC of the same unrelated donor prior to PBSC transplantation OR from the same unrelated bone marrow donor after bone marrow transplantation. Eligible patients receive the first donor lymphocyte infusion (DLI) over 30 minutes. Patients with disease progression and no graft versus host disease (GVHD) at greater than day 28 after the first DLI OR persistent/progressive disease, mixed chimerism, and no GVHD at day 65 after the first DLI receive a second DLI. Patients with disease progression and no GVHD at greater than day 28 after the second DLI OR persistent disease, mixed chimerism, and no GVHD at day 65 after the second DLI receive a third DLI. Patients are followed weekly until day 90, then at 4, 6, 12, 18, and 24 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 2 years.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven hematologic malignancy including, but not limited to, the following: Non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia, or Hodgkin's disease; Failed prior front-line therapy; No rapidly progressive intermediate or high grade NHL; Multiple myeloma Prior chemotherapy required; Consolidation of prior autografting allowed; Acute myeloid leukemia (AML) or acute lymphoblastic leukemia; Incomplete remission and prior cytotoxic chemotherapy at some point before transplantation required; Molecular or early relapse allowed if donor available; Persistent or refractory disease considered on a case-by-case basis; Chronic myelogenous leukemia (CML); Chronic or accelerated phase allowed; Patients who have received autografts after high-dose therapy or who have undergone intensive chemotherapy for either peripheral blood stem cell mobilization or treatment of advanced CML eligible if in complete remission, chronic phase, or accelerated phase Myelodysplastic syndrome (MDS); All patients with MDS eligible except those with frank AML (greater than 30% blasts in bone marrow aspirate) OR Diagnosis of renal cell carcinoma
• Over age 50: Must have a hematologic disease that is treatable by allogeneic stem cell transplantation (alloSCT)
• Age 50 and under: Patients who have hematologic malignancy that is treatable by alloSCT and who, through preexisting medical conditions or prior therapy, are considered at high risk for regimen-related toxicity associated with conventional transplantation
• Availability of a 10 antigen (A, B, C, DR-B, and DR-Q loci) HLA-matched unrelated donor
• Any active CNS disease

[A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.]

--Prior/Concurrent Therapy--

• See Disease Characteristics

--Patient Characteristics--

• Age: See Disease Characteristics
• Performance status: Karnofsky 50-100%
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics
• Hepatic: Significant elevations in bilirubin, SGOT, and SGPT allowed on a case-by-case basis; No synthetic dysfunction or severe cirrhosis
• Renal: Not specified
• Cardiovascular: Cardiac ejection fraction at least 30%; No cardiac failure requiring therapy; No poorly controlled hypertension on multiple antihypertensives
• Pulmonary: DLCO at least 35% predicted; No requirement for supplementary continuous oxygen
• Other: Not pregnant or nursing; Fertile patients must use effective contraception during and for 1 year after study; HIV negative

California
      Cancer Center and Beckman Research Institute, City of Hope, Los Angeles,  California,  91010-3000,  United States
      Stanford University, Stanford,  California,  94305,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80010,  United States
Texas
      Baylor University Medical Center, Dallas,  Texas,  75246,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States
Germany
      Universitaet Leipzig, Leipzig,  D-04103,  Germany

Study chairs or principal investigators

Michael Maris,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000067770; FHCRC-1463.00; NCI-G00-1762
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005799
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08