Autotransplantation for Chronic Myelogenous Leukemia (CML) Followed by Immunotherapy With Ex-Vivo Expanded Autologous T Cells
- Determine the feasibility of ex vivo expansion and reinfusion of autologous CD4+ T
cells after interferon therapy or high-dose chemotherapy with CD34-selected autologous
peripheral blood stem cell rescue in patients with chronic phase chronic myelogenous
- Determine the frequency of hematologic, cytogenetic, and molecular remissions of CML
following infusion of ex vivo expanded T cells.
OUTLINE: Patients undergo mononuclear cell leukapheresis to obtain T cells for ex-vivo
expansion, preferably before they receive interferon alfa subcutaneously (SC) daily on a
At least 1 month after interferon is stopped, mobilization chemotherapy is administered.
Patients receive cyclophosphamide IV over 12 hours on day 0, etoposide IV over 2 hours on
day 1, sargramostim (GM-CSF) SC on days 3 and 4, and filgrastim (G-CSF) SC beginning on day
5. Peripheral blood stem cells (PBSC) are collected by leukapheresis when blood cell counts
Approximately 2-3 weeks later, high-dose chemotherapy begins. Patients receive gemcitabine
IV over 100 minutes on day -5, carmustine IV over 2 hours on day -2, followed 6 hours later
by gemcitabine IV again, and melphalan IV over 20 minutes on day -1. CD34 selected PBSCs are
infused on day 0, at least 18 hours after melphalan administration. Patients receive GM-CSF
SC beginning on day 1 and continuing until blood cell counts recover.
Patients then receive ex vivo expanded autologous T cells on day 14 after
autotransplantation. Interferon alfa is administered three times a week starting about 3
months after transplantation.
Patients who only receive expanded T cells, without high-dose chemotherapy and
autotransplantation, but show no response after 3 months, may proceed to autotransplantation
followed by a second ex vivo expanded T-cell infusion.
Patients are followed at 1, 2, 3, 6, 9, and 12 months, then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 7-22 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Response (i.e., major cytogenetic or molecular response) within 12 months after completion of study therapy
Aaron P. Rapoport, MD
University of Maryland Greenebaum Cancer Center
United States: Food and Drug Administration
|Greenebaum Cancer Center at University of Maryland Medical Center||Baltimore, Maryland 21201|