A Phase I Study To Evaluate The Safety Of Cellular Immunotherapy Using Genetically Modified Autologous Cd20-Specific Cd8+ T Cell Clones For Patients With Relapsed Cd20+ Indolent Lymphomas
- Determine the safety and toxicity of cellular immunotherapy with autologous CD8+
cytotoxic T-lymphocyte clones after chemotherapy comprising cyclophosphamide,
vincristine, and prednisone in patients with relapsed or refractory CD20+ indolent
lymphomas or mantle cell lymphoma.
- Determine the duration of in vivo persistence of adoptively transferred CD20-specific
CD8+ cytotoxic T-lymphocyte clones in the absence and presence of subcutaneous
interleukin-2 in these patients.
- Assess the trafficking of CD8+ cytotoxic T-lymphocyte clones to lymph nodes in these
patients treated with this regimen.
- Determine immune response and tumor response in patients treated with this regimen.
OUTLINE: This is an open-label, pilot study.
- Leukapheresis: Patients undergo leukapheresis. Selected CD20-specific CD8+ cells are
cultured to expand the cytotoxic T lymphocytes (CTL), which are then cloned.
Patients receive oral cyclophosphamide and oral prednisone on days 1-5 and vincristine IV on
day 1. Courses repeat every 3-4 weeks for a total of 6 courses.
- Immune cell infusion:
Beginning 4 weeks after the last course of chemotherapy (and lymph nodes ≤ 5 cm diameter or
≤ 5,000 circulating CD20+ lymphocytes/mm^3), patients receive autologous CD8+ CTL clones IV
over 30 minutes. Courses repeat every 2-5 days for a total of 3 courses in the absence of
disease progression or unacceptable toxicity. The last 6 patients receive interleukin-2
subcutaneously every 12 hours for 14 days, beginning 2 hours after the last infusion of CD8+
After course 2 or 3 of immune cells, all patients undergo surgical lymph node biopsy to
determine if immune cells are moving to the lymph nodes.
Patients are followed monthly for 1 year and then annually for 2 years.
PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 4 years.
Masking: Open Label, Primary Purpose: Treatment
Safety and toxicity by NCI CTC toxicity scale in patients w/ recurr. or refract. CD20+ follicular lymphoma who are not candidates for high dose chemoradiotx and stem cell transplant during each infusion, weekly for 4 wks and then monthly for a yr
Oliver W. Press, MD, PhD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|City of Hope Comprehensive Cancer Center||Duarte, California 91010|
|University of Washington School of Medicine||Seattle, Washington 98195|