Expired Study
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Bethesda, Maryland 20892


Purpose:

RATIONALE: Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment with donor immune cells may prevent this from happening. PURPOSE: Phase I/II trial to study the effectiveness of treated donor immune cells in preventing graft-versus-host disease following peripheral stem cell transplantation in treating patients who have hematologic cancer.


Study summary:

OBJECTIVES: Phase I - Determine the safety and feasibility of activated donor CD4+ T cells of the Th2 cytokine phenotype (donor Th2 cells) for the prevention of graft-vs-host disease (GVHD) after non-myeloablative, HLA-matched allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies. Phase II - Determine the incidence and severity of acute GVHD in patients treated with this regimen. - Compare the incidence and severity of acute GVHD in patients treated with Th2 cells vs the initial cohort of patients that do not receive Th2 cells. - Determine, preliminarily, whether treatment with Th2 cells reduces acute GVHD in these patients. OUTLINE: This is a dose-escalation study of donor Th2 cells. Phase I - Harvest and activation: Donor lymphocytes from an HLA-matched sibling donor are harvested and cultured in vitro under conditions that promote activation of donor CD4+ T cells of the Th2 cytokine phenotype (donor Th2 cells). Immediately after lymphocyte harvest, donors receive filgrastim (G-CSF) subcutaneously (SC) daily for 5-7 days. On days 5 and 6 of G-CSF regimen, allogeneic peripheral blood stem cells (PBSC) from the same donor are harvested and selected primarily for CD4+ T cells. - Induction: Patients receive fludarabine IV over 30 minutes, etoposide IV continuously, doxorubicin IV continuously, and vincristine IV continuously on days 1-3; oral prednisone on days 1-4; and cyclophosphamide IV over 30 minutes on day 4. Patients receive G-CSF SC daily beginning on day 5 and continuing until blood counts recover. Patients with CD4+ counts below 50/mm^3 at day 15-21 of the first induction course proceed directly to transplantation preparative chemotherapy. Patients with CD4+ counts greater than 50/mm^3 at day 15-21 of the first induction course continue induction therapy every 3 weeks for a maximum of 3 courses and then proceed to transplantation preparative chemotherapy. Patients who develop progressive disease during the first course proceed to transplantation preparative chemotherapy. - Transplantation preparative chemotherapy: Patients receive fludarabine IV over 15-30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3. - Graft-versus-host disease (GVHD) chemoprophylaxis: Beginning on day -1, patients receive cyclosporine IV over 1-2 hours every 12 hours until day 13 after transplantation or until establishment of oral intake. Patients receive oral cyclosporine every 12 hours on days 14-100 followed by tapering doses of cyclosporine on days 101-180. - Allogeneic PBSC transplantation: PBSC are reinfused on day 0. Patients receive G-CSF SC daily beginning immediately after transplantation and continuing until blood counts recover. - GVHD prophylaxis: Patients receive donor Th2 cells IV on day 1. Cohorts of 3 to 6 patients receive 1 of 3 dose levels of donor Th2 cells to determine the maximum tolerated dose (MTD). The MTD is defined as the dose at which no more than 1 of 6 patients experience dose-limiting toxicity and no more than 2 of 6 patients experience grade II or greater GVHD. Phase II - Patients receive treatment as in phase I with donor Th2 cells at the MTD. Patients are followed at days 140, 180, 290, and 365, every 6 months for 1 year, and then annually for 3 years. PROJECTED ACCRUAL: A maximum of 124 patients will be accrued for this study within 2.5 years.


Criteria:

DISEASE CHARACTERISTICS: - One of the following diagnoses: - Chronic lymphocytic leukemia - Relapse after fludarabine OR - Incomplete response after salvage regimen - Hodgkin's lymphoma, non-Hodgkin's lymphoma (all types, including mantle cell lymphoma), or multiple myeloma - Primary treatment failure OR - Relapse after autologous peripheral blood stem cell transplantation OR - Incomplete response after salvage regimen - Acute myelogenous leukemia - First, second, or third complete remission (CR) OR - Any relapse with fewer than 10% blasts (marrow and blood) - Acute lymphocytic leukemia - Second or third CR OR - Any relapse with fewer than 10% blasts (marrow and blood) - Myelodysplastic syndromes - Refractory anemia with excess blasts (RAEB) OR - RAEB in transformation with fewer than 10% blasts (marrow and blood) after induction chemotherapy - Chronic myelogenous leukemia - Chronic phase OR - Accelerated phase - Availability of 6/6 antigen (A, B, and DR loci) HLA-matched sibling donor - No active CNS disease - Prior CNS disease allowed if in CR after appropriate treatment PATIENT CHARACTERISTICS: Age: - 18 to 75 Performance status: - Karnofsky 70-100% Life expectancy: - More than 3 months Hematopoietic: - See Disease Characteristics Hepatic: - Bilirubin less than 2.5 mg/dL - ALT and AST no greater than 2.5 times upper limit of normal (unless due to tumor involvement) - Hepatitis B or C surface antigen negative Renal: - Creatinine no greater than 1.5 mg/dL OR - Creatinine clearance at least 60 mL/min Cardiovascular: - LVEF at least 45% by MUGA or echocardiogram Pulmonary: - DLCO greater than 50% of predicted Other: - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No active infection - HIV negative - No prior psychiatric disorder that would preclude compliance PRIOR CONCURRENT THERAPY: Biologic: - See Disease Characteristics Chemotherapy: - See Disease Characteristics Endocrine: - No concurrent corticosteroids Radiotherapy: - Not specified Surgery: - Not specified


NCT ID:

NCT00019851


Primary Contact:

Study Chair
Michael R. Bishop, MD
National Cancer Institute (NCI)


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: September 20, 2017

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