Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following Fludarabine Lymphodepletion for Patients With Metastatic Melanoma
18 Years
75 Years
Both
Melanoma (Skin)
Trial Information
Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following Fludarabine Lymphodepletion for Patients With Metastatic Melanoma
OBJECTIVES:
Primary
- Determine the safety and toxicity of adoptive immunotherapy comprising autologous CD8+
antigen-specific cytotoxic T-lymphocyte (CTL) clones after fludarabine in patients with
stage IV melanoma.
- Determine the duration of in vivo persistence of these CTL clones in these patients.
Secondary
- Determine the antitumor effect of this regimen in these patients.
OUTLINE: This is an open-label, nonrandomized study.
Patients undergo leukapheresis or weekly phlebotomy for the collection of peripheral blood
mononuclear cells from which autologous antigen-specific CD8+ cytotoxic T-lymphocyte (CTL)
clones are generated. Patients receive autologous antigen-specific CD8+ CTL clones IV over
30-60 minutes on days 0 and 21 in the absence of rapid disease progression or unacceptable
toxicity. Patients also receive fludarabine IV once daily on days 14-18.
Patients are followed for up to 1 year.
PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 3 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed metastatic melanoma
- Stage IV disease
- HLA-A2 or -A3-expressing disease
- Bidimensionally measurable residual disease by palpation or radiographic imaging
(e.g., x-ray or CT scan)
- No CNS metastases
- Previously treated CNS involvement allowed provided there is no evidence of CNS
disease at least 2 months after completion of therapy
PATIENT CHARACTERISTICS:
Age
- 18 to 75
Performance status
- Karnofsky 80-100%
Life expectancy
- More than 6 months
Hematopoietic
- Platelet count > 100,000/mm^3
- Absolute neutrophil count > 2,000/mm^3
Hepatic
- SGOT no greater than 3 times upper limit of normal
- Bilirubin no greater than 1.6 mg/dL
- INR no greater than 1.5 times normal
Renal
- Creatinine no greater than 2.0 mg/dL OR
- Creatinine clearance at least 60 mL/min
Cardiovascular
- No congestive heart failure
- No clinically significant hypotension
- No symptoms of coronary artery disease
- No cardiac arrhythmia by EKG requiring drug therapy
Pulmonary
- No clinically significant pulmonary dysfunction
- FEV_1 at least 1.0 L*
- DLCO at least 45%* NOTE: *For patients with a history of pulmonary dysfunction
Immunologic
- No active infection
- No oral temperature greater than 38.2°C within the past 48 hours
- No systemic infection requiring chronic maintenance or suppressive therapy
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent immunotherapy (e.g., interleukins, interferons, melanoma vaccines, IV
immunoglobulins, expanded polyclonal tumor-infiltrating lymphocytes, or
lymphokine-activated killer therapy)
Chemotherapy
- At least 3 weeks since prior chemotherapy (standard or experimental)
Endocrine therapy
- No concurrent steroids
Radiotherapy
- At least 3 weeks since prior radiotherapy
Surgery
- Not specified
Other
- At least 3 weeks since prior immunosuppressive therapy
- No concurrent pentoxifylline
- No other concurrent investigational agents
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Cassian Yee, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center
Authority:
United States: Federal Government
Study ID:
1796.00
NCT ID:
NCT00317759
Start Date:
May 2003
Completion Date:
October 2008
Related Keywords:
- Melanoma (Skin)
- stage IV melanoma
- recurrent melanoma
- Melanoma
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
