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Prevention of Graft-Versus-Host Disease Following Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

2014-08-27 03:56:47 | BioPortfolio

Summary

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.

Description

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.

Study Design

Primary Purpose: Supportive Care

Conditions

Graft Versus Host Disease

Intervention

filgrastim, therapeutic allogeneic lymphocytes, cyclophosphamide, cyclosporine, doxorubicin hydrochloride, etoposide, fludarabine phosphate, prednisone, vincristine sulfate, peripheral blood stem cell transplantation

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda
Maryland
United States
20892-1182

Status

Active, not recruiting

Source

National Cancer Institute (NCI)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:56:47-0400

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Medical and Biotech [MESH] Definitions

A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.

A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.

A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS.

A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.

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