Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen Specific T Cell Clones Targeting Cancer Testis Antigens 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 Targeting Cancer Testis Antigens for Patients With Metastatic Melanoma
OBJECTIVES:
Primary
- Determine the safety and toxicity of cellular adoptive immunotherapy comprising
autologous CD8+ cytotoxic T-lymphocyte clones targeting cancer-testis antigens in
patients with metastatic melanoma.
- Determine the duration of in vivo persistence of this therapy in these patients.
Secondary
- Evaluate the antitumor effects of this therapy in these patients.
OUTLINE: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells and
then CD8+ cytotoxic T-lymphocyte (CTL) clones are generated ex vivo. Patients receive
cellular adoptive immunotherapy comprising autologous CD8+ CTL clones targeting cancer
testis antigens IV over 30 minutes on day 1. Patients also receive interleukin-2
subcutaneously every 12 hours on days 1-14 of courses 2-4. Treatment repeats every 3 weeks
for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who
demonstrate a clinical response after completion of the fourth course are eligible to
receive additional T-cell infusions.
Patients are followed for 9 months.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 3 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed metastatic melanoma
- Stage IV disease
- HLA-A1, -A2, and -A3 positive
- MAGE-1 or -3 positive by histology
- Bidimensionally measurable disease by palpation on clinical examination, x-ray, or CT
scan
- No CNS metastases
PATIENT CHARACTERISTICS:
Age
- 18 to 75
Performance status
- Karnofsky 80-100%
Life expectancy
- More than 6 months
Hematopoietic
- Not specified
Hepatic
- Bilirubin ≤ 1.6 mg/dL
- SGOT ≤ 3 times upper limit of normal
- PT ≤ 1.5 times control
Renal
- Creatinine ≤ 2.0 mg/dL
- Calcium ≤ 12 mg/dL
Cardiovascular
- No congestive heart failure
- No clinically significant hypotension
- No symptoms of coronary artery disease
- No cardiac arrhythmias on electrocardiogram requiring drug therapy
- Patients with prior cardiovascular disease or the presence of any of the above
abnormalities undergo a cardiac evaluation, which may include a stress test and/or
echocardiogram
Pulmonary
- No clinically significant pulmonary dysfunction by medical history or physical
examination
- FEV_1 ≥ 60% of normal
- DLCO ≥ 55% (corrected for hemoglobin)
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No retinitis or choroiditis
- No active infections or oral temperature greater than 38.2 degrees Celsius within the
past 72 hours
- No systemic infection requiring chronic maintenance or suppressive therapy
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No other concurrent immunotherapy (e.g., other interleukins, interferons, melanoma
vaccines, intravenous immunoglobulin, or expanded polyclonal tumor-infiltrating
lymphocytes or lymphokine-activated killer cell therapy)
Chemotherapy
- At least 3 weeks since prior standard or experimental chemotherapy
- 1-2 courses of prior cytoreductive chemotherapy for bulky disease allowed
Endocrine therapy
- No concurrent systemic steroids (except for toxicity management)
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:
Study Chair
Investigator Affiliation:
Fred Hutchinson Cancer Research Center
Authority:
United States: Federal Government
Study ID:
1588.00
NCT ID:
NCT00045149
Start Date:
October 2002
Completion Date:
June 2005
Related Keywords:
- Melanoma (Skin)
- recurrent melanoma
- stage IV melanoma
- Melanoma
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
