Total-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

University of Texas Southwestern Medical Center

Overview

RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining total-body irradiation with fludarabine and donor peripheral stem cell transplantation in treating patients who have hematologic cancer.

OBJECTIVES: * Determine the response rate and duration of response in patients with low-risk hematologic malignancies treated with low-dose total-body irradiation (TBI) and fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a slow immunosuppression taper and donor leukocyte infusions (DLI). * Determine the response rate and duration of response in patients with high-risk hematologic malignancies treated with low-dose TBI and fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a faster immunosuppression taper and DLI. * Determine the incidence and extent of graft-versus-host disease, regimen-related toxicity, and engraftment in patients treated with these regimens. * Assess the quality of life of patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 groups (high-risk vs low-risk hematologic malignancy). The high-risk group includes acute myelogenous leukemia, myelodysplastic syndromes, accelerated phase chronic myelogenous leukemia (CML), second chronic phase CML, and non-Hodgkin's lymphoma. The low-risk group includes Hodgkin's lymphoma, first chronic phase CML, multiple myeloma, and chronic lymphocytic leukemia. Patients receive fludarabine IV on days -4 to -2. Patients undergo total-body irradiation on day 0 followed by allogeneic stem cell transplantation. Patients also receive oral mycophenolate mofetil on days 0-28. High-risk patients receive oral cyclosporine twice daily on days -2 to day 60. Patients with persistent disease, T-cell chimerism, and no graft-vs-host disease (GVHD) on day 90 receive up to 3 doses of donor leukocyte infusion (DLI) over the next 4 months. Low-risk patients receive oral cyclosporine twice daily on days -2 to day 150. Patients with persistent disease, T-cell chimerism, and no GVHD on day 180 receive up to 3 doses of DLI over the next 4 months. Quality of life is assessed at baseline and at 1, 3, 6, 9, 12, 18, and 24 months. Patients are followed at 1, 3, 6, 9, and 12 months and then annually for 2 years. PROJECTED ACCRUAL: A total of 120 patients (60 per group) will be accrued for this study.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Masking

NONE

Conditions

Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases

Interventions

therapeutic allogeneic lymphocytesBIOLOGICAL

cyclosporineDRUG

fludarabine phosphateDRUG

mycophenolate mofetilDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Diagnosis of one of the following hematologic malignancies: * Chronic myelogenous leukemia (CML) * First or second chronic phase * Accelerated phase * Acute myelogenous leukemia (AML) * At least second remission * First remission allowed if poor-risk features are present (complex chromosome karyotype, abnormalities of chromosomes, especially 5 or 7, 12p-, +13, +8, t\[9:11\]) * Myelodysplastic syndromes (MDS) * Intermediate- or high-risk disease by the prognostic scoring system * Multiple myeloma (MM) * Hodgkin's lymphoma * Second or greater relapse * First relapse allowed if disease-free interval is less than 1 year * Ineligible for autologous transplantation * Non-Hodgkin's lymphoma (NHL) * Grade III follicular large cell (relapsed after one course of prior chemotherapy) * Diffuse large cell (relapsed after one course of prior chemotherapy) * Mantle cell * Chronic lymphocytic leukemia (CLL) * Relapsed after at least 1 course of prior therapy * Must have 6 out of 6 HLA A-, B-, and DR- identical sibling donor PATIENT CHARACTERISTICS: Age * 18 to 75 for patients with MM * 50 to 75 for patients with CML, AML, MDS, Hodgkin's lymphoma, NHL, or CLL * 18 to 49 for patients with CML, AML, MDS, Hodgkin's lymphoma, NHL, or CLL who are considered eligible for an allogeneic bone marrow transplantation (BMT) but do not meet institutional criteria for a standard allogeneic BMT Performance status * Zubrod 0-2 Life expectancy * At least 6 months Hematopoietic * Not specified Hepatic * Bilirubin no greater than 3 mg/dL Renal * Creatinine no greater than 2 mg/dL Cardiovascular * LVEF at least 40% by MUGA or echocardiogram Pulmonary * DLCO at least 50% of predicted Other * HIV negative * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No recent history of drug or alcohol abuse * No other prior malignancy except basal cell skin cancer * No uncontrolled bacterial, viral, fungal, or parasitic infections PRIOR CONCURRENT THERAPY: Biologic therapy * Prior autologous transplantation allowed if disease progression occurred * No prior or concurrent tandem autologous transplantation followed by non-myeloablative-allograft protocol Chemotherapy * See Disease Characteristics Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified

Locations (14)

Rocky Mountain Cancer Centers - Denver Midtown

Denver, Colorado, United States

Florida Hospital Cancer Institute

Orlando, Florida, United States

Data from ClinicalTrials.gov

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