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
N/A
N/A
Both
Leukemia, Lymphoma
Trial Information
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
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
- Chemotherapy:
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+
CTL clones.
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Immunohistopathologically documented relapsed or refractory CD20+ indolent lymphomas
or mantle cell lymphoma
- Indolent B-cell lymphomas including any of the following subtypes:
- Follicular lymphoma (grade I, II, or III)
- Small lymphocytic lymphoma or chronic lymphocytic leukemia
- Marginal zone lymphoma (splenic, nodal, and extra-nodal)
- Lymphoplasmacytoid lymphoma
- Ineligible for or unwilling to participate in other FHCRC/UWMC protocols
- Serological evidence of prior exposure to Epstein-Barr virus
- Must agree to undergo peripheral blood drawing, bone marrow biopsy, lymph node
biopsy, and nuclear medicine imaging
- Must agree to cytoreductive chemotherapy if necessary to reduce lymph nodes to < 5 cm
in diameter or circulating B lymphocyte counts to < 5,000/mm^3
- No pulmonary involvement
- No CNS involvement
PATIENT CHARACTERISTICS:
Age:
- Any age
Performance status:
- Not specified
Life expectancy:
- At least 90 days
Hematopoietic:
- Not specified
Hepatic:
- No active hepatitis B infection
Renal:
- Not specified
Other:
- No HIV positivity
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No history of hypersensitivity reactions to murine proteins
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 4 months since prior rituximab, tositumomab, or ibritumomab
- No prior allogeneic stem cell transplantation
- No other concurrent immunotherapy (e.g., interferons, vaccines, or other cellular
products)
Chemotherapy:
- At least 2 years since prior fludarabine or cladribine
- At least 4 weeks since prior chemotherapy and recovered
Endocrine therapy:
- No concurrent systemic corticosteroids except to treat toxicity from chemotherapy or
cellular immunotherapy
Radiotherapy:
- Not specified
Surgery:
- Not specified
Other:
- At least 4 weeks since prior immunosuppressive therapy and recovered
- No concurrent pentoxifylline
- No other concurrent investigational agents
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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
Safety Issue:
Yes
Principal Investigator
Oliver W. Press, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Fred Hutchinson Cancer Research Center
Authority:
United States: Federal Government
Study ID:
1503.00
NCT ID:
NCT00012207
Start Date:
September 2000
Completion Date:
July 2010
Related Keywords:
- Leukemia
- Lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- refractory chronic lymphocytic leukemia
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
Name | Location |
|---|---|
| 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 |
