A Phase I-II Trial of Antigen-Pulsed Autologous Dendritic Cells for Induction of Anti-Tumor Immunity in Patients Completing Lymphadenectomy for Metastatic Melanoma
18 Years
75 Years
Both
Melanoma (Skin)
Trial Information
A Phase I-II Trial of Antigen-Pulsed Autologous Dendritic Cells for Induction of Anti-Tumor Immunity in Patients Completing Lymphadenectomy for Metastatic Melanoma
OBJECTIVES: I. Determine the safety and toxicity of intravenous injections of autologous
cultured dendritic cells pulsed with either gp100 and tyrosinase peptides or autologous
melanoma tumor cell lysates in patients with metastatic melanoma. II. Determine whether
treatment with melanoma tumor antigen pulsed autologous dendritic cells results in increased
in vitro tumor specific cytotoxic T-cell responses. III. Determine whether this treatment
can induce positive skin test responses to tumor antigens. IV. Evaluate the disease free and
overall survival of these patients.
OUTLINE: This is a randomized, dose escalation study. Approximately 1-2 weeks following
surgical lymphadenectomy, patients undergo leukapheresis to collect dendritic cells and are
then divided into 3 groups. Group A consists of patients without adequate tumor for
preparation of tumor lysate and who have tumors that express tyrosinase or gp100 with types
HLA-A1, A2, or A3. Group B consists of the patients who have adequate tumor for lysate
preparation but who do not type for HLA-A1, A2, or A3 (required for the peptide pulsed
protocol). Group C are the patients with adequate tumor who are eligible for the peptide
pulsed protocol. Group A patients receive autologous dendritic cells pulsed with appropriate
peptide antigens. Group B patients are treated with autologous dendritic cells pulsed with
autologous tumor cell lysates. Group C patients are randomized to receive dendritic cells
pulsed with either peptide antigens or tumor lysate. All patients are administered
intravenous active immunotherapy for 4 monthly intervals. The dose of the immunizations is
escalated for each cohort of three patients that is accrued in each of the groups mentioned
above. Each immunization at each dose level is followed by three days of interleukin-2
administered subcutaneously twice daily. Patients are followed at least 5 years for
survival.
PROJECTED ACCRUAL: There will be 100 patients accrued in this study over 2 years. There will
be 50, 20, and 30 patients in groups A, B, and C, respectively.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically confirmed metastatic melanoma involving cervical,
axillary, inguinal, groin, or iliac lymph nodes All gross disease is resected at the time
of surgical lymphadenectomy No distant metastases
PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: ECOG 0-1 Life expectancy: At
least 6 months Hematopoietic: Platelet count at least 100,000/mm3 Hemoglobin at least 8
g/dL Hepatic: Bilirubin no greater than 1.4 mg/dL AST or ALT no greater than 1.5 times
normal No active hepatitis Renal: Creatinine no greater than 1.4 mg/dL Cardiovascular: No
congestive heart failure, unstable angina, or current symptomatic arrhythmias Other: HIV
negative No autoimmune diseases (e.g., lupus erythematosus, multiple sclerosis, or
ankylosing spondylitis) No condition that would be considered as a contraindication for
surgery Not pregnant or nursing Adequate contraception required for all fertile patients
PRIOR CONCURRENT THERAPY: At least 4 weeks since prior therapy for melanoma Biologic
therapy: At least 3 months since prior interferon therapy Chemotherapy: No active
immunosuppression due to prior chemotherapy Endocrine therapy: No active immunosuppression
due to steroid therapy Radiotherapy: Not specified Surgery: Not specified
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Principal Investigator
Hilliard F. Seigler, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Duke Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000066097
NCT ID:
NCT00003229
Start Date:
July 1997
Completion Date:
February 2005
Related Keywords:
- Melanoma (Skin)
- stage IV melanoma
- recurrent melanoma
- Melanoma
Name | Location |
|---|---|
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Cancer Center, University of Virginia HSC | Charlottesville, Virginia 22908 |
