A Phase IIa Study Testing the Biologic Activity and Safety of Autologous Renal Cell Carcinoma Total mRNA and huCD40L Newly Diagnosed Stage IV Renal Cell Carcinoma
- Determine the biological and clinical responses, in terms of measured T-cell responses,
of two different induction vaccination regimens comprising autologous dendritic cells
transfected with autologous tumor mRNA and human CD40 ligand in patients with newly
diagnosed stage IV clear cell renal cell carcinoma.
- Determine safety of multiple administrations of this vaccine in these patients.
- Determine the overall feasibility of these regimens, in terms of ability to produce
vaccine within 13 weeks from the first leukapheresis.
- Determine the antitumor activity of this vaccine, in terms of objective response,
progression-free survival, and overall survival in these patients.
- Determine the applicability of several new assays characterizing the immunogenicity of
the vaccine as potency assays or surrogate parameters for biologic or clinical activity
in these patients.
- Correlate the delayed type hypersensitivity reactions with clinical activity of T-cell
immunity in patients treated with this regimen.
OUTLINE: This is an open-label, multicenter study.
All patients undergo nephrectomy or excisional biopsy or metastectomy to obtain and generate
autologous tumor mRNA. Approximately 4-8 weeks after surgery, patients undergo leukapheresis
to obtain peripheral blood mononuclear cells for the generation of dendritic cells (DC). The
DC are then transfected with autologous tumor mRNA and human CD40 ligand mRNA to produce a
vaccine. Patients are then assigned to 1 of 2 treatment groups.
- Group 1: Patients receive vaccine intradermally once every 14 days for a total of 5
injections followed by once every 28 days for 4 injections, and then once every 3
months in the absence of disease progression or unacceptable toxicity.
- Group 2: Patients receive vaccine intradermally once every 42 days for a total of 5
injections and then every 3 months in the absence of disease progression or
Patients undergo blood collection periodically during study for biomarker correlative
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: Approximately 26 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
T-cell response to RNA-loaded dendritic cells as assessed by the ELISpot assay on blood cells at screening, baseline, weeks 6 and 14 and years 1 and 2 after first vaccination, and at completion of study treatment
Fairooz F. Kabbinavar, MD
Jonsson Comprehensive Cancer Center
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|