Vaccination of HLA-A1 and/or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide-Loaded Autologous Dendritic Cells With Prior Depletion of CD25-Positive Cells Using Denileukin Difitox (ONTAK)
18 Years
N/A
Both
Melanoma (Skin)
Trial Information
Vaccination of HLA-A1 and/or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide-Loaded Autologous Dendritic Cells With Prior Depletion of CD25-Positive Cells Using Denileukin Difitox (ONTAK)
OBJECTIVES:
- Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor
and influenza antigen peptides with or without ex vivo CD40-ligand and denileukin
diftitox, in terms of tumor-specific T-cell response, in patients with HLA-A1- and/or
HLA-A2.1-positive stage III or IV melanoma.
- Determine the safety and tolerability of these vaccinations in these patients.
- Determine tumor response in patients treated with these vaccinations.
OUTLINE:
- Phase I (Administration of denileukin diftitox and vaccinations #1 to #4): Patients
undergo leukapheresis for collection of peripheral blood mononuclear cells (PMBC). PBMC
are processed for the generation of dendritic cells (DC) to be used for vaccinations.
DC are pulsed with HLA-A1- and HLA-A2.1-restricted peptides derived from
melanoma-associated tumor antigens. DC are pulsed with or without ex vivo treatment
with CD40-ligand. Patients receive denileukin diftitox IV for 3 consecutive days before
the first vaccination. Patients receive 4 pulsed DC vaccinations subcutaneously (SC) on
days 1, 14, 42, and 70 in the absence of disease progression or unacceptable toxicity.
Patients who show a tumor response (at least stable disease) may receive vaccination #5 and
further booster vaccinations.
- Phase II: DC are generated and pulsed as in phase I. Patients receive up to 6
additional booster pulsed DC vaccinations SC on days 126, 184, 268, 356, 520, and 692
in the absence of disease progession or unacceptable toxicity.
Patients are followed for 10 years.
PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed locoregional or metastatic cutaneous malignant melanoma
- Stage III or IV disease
- Stage III: pT4b, N0, M0 (satellite metastases) or any pT, N1 or pT, N1 or
N2a-c, M0 (lymph node metastases or in transit intralymphatic metastases)
- Stage IV: any pT, N1-2, M1a-b
- Surgically incurable
- Incurable with standard treatment (i.e., localized chemotherapy/limb
perfusion for stage III, systemic chemotherapy for stage IV)
- Unidimensionally or bidimensionally measurable disease by physical examination (e.g.,
cutaneous metastases) and/or non-invasive radiologic procedures NOTE: Stage III
lesions may be measurable lymph nodes after incomplete resection and/or inoperable in
transit metastases
- HLA-A1 and/or HLA-A2 expression by serologic HLA typing
- HLA-A2.01 subtype must be confirmed by polymerase chain reaction on genomic DNA
obtained from peripheral blood mononuclear cells
- No active CNS metastases
- Previously treated CNS metastases (e.g., excision of a single metastasis)
allowed if no active disease present by CT scan or MRI
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- Karnofsky 60-100%
Life expectancy
- At least 6 months
Hematopoietic
- WBC greater than 2,500/mm^3
- Neutrophil count greater than 1,000/mm^3
- Lymphocyte count greater than 700/mm^3
- Platelet count greater than 75,000/mm^3
- Hemoglobin greater than 9 g/dL
- No bleeding disorders
Hepatic
- Bilirubin less than 2.0 mg/dL
- No hepatitis B or C
Renal
- Creatinine less than 2.5 mg/dL
Cardiovascular
- No clinically significant heart disease
Pulmonary
- No clinically significant respiratory disease
Immunologic
- No active systemic infection
- No immunodeficiency disease
- No evidence of HIV-1, HIV-2, or human T-cell lymphocytic virus-1
- No active autoimmune disease including, but not limited to:
- Lupus erythematosus
- Autoimmune thyroiditis or uveitis
- Multiple sclerosis
- Inflammatory bowel disease NOTE: Vitiligo allowed
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 weeks after study
participation
- No organic brain syndrome or significant psychiatric abnormality that would preclude
study participation and follow-up
- No contraindication to leukapheresis
- No other active malignant neoplasms
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior systemic immunotherapy
- No concurrent immunotherapy during and for 2 weeks after last vaccination
Chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g.,
fotemustine])
- No concurrent chemotherapy during and for 2 weeks after last vaccination
Endocrine therapy
- No concurrent corticosteroids during and for 2 weeks after last vaccination
Radiotherapy
- No prior radiotherapy to the spleen
- Concurrent palliative radiotherapy allowed for selected metastases (e.g., pain or
local complications such as compression)
Surgery
- See Disease Characteristics
- Recovered from prior surgery
- No prior splenectomy
- No prior organ allografts
- Concurrent surgery of selected metastases (e.g., pain or local complications such as
compression) allowed
Other
- No other concurrent investigational drugs during and for 2 weeks after last
vaccination
- No concurrent paramedical substance during and for 2 weeks after last vaccination
- No concurrent participation or intent to participate in another clinical trial
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety and tolerability as assessed by clinical and laboratory evaluation at every visit
Safety Issue:
Yes
Principal Investigator
Gerold Schuler
Investigator Role:
Study Chair
Investigator Affiliation:
Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
Authority:
United States: Federal Government
Study ID:
CDR0000270762
NCT ID:
NCT00056134
Start Date:
October 2002
Completion Date:
Related Keywords:
- Melanoma (Skin)
- recurrent melanoma
- stage IV melanoma
- stage IIIA melanoma
- stage IIIB melanoma
- stage IIIC melanoma
- Melanoma
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