Clinical trial NCT00197860: Dendritic Cell Based Therapy of Renal Cell Carcinoma
Official title: Vaccination With Autologous Dendritic Cells Pulsed With Tumor Antigens for Treatment of Patients With Renal Cell Carcinoma.A Phase I/II Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Renal Cell Carcinoma
Keywords: dendritic cell
vaccine
renal cell carcinoma
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2005-09-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to show if vaccination with autologous dendritic cells pulsed with peptides or tumor lysate in combination with adjuvant cytokines can induce a measurable immune response in patients with metastatic renal cell carcinoma, and to evaluate the clinical effect (objective response rate) of the vaccination regime.

Detailed description: Eligible patients receive vaccination with tumor antigen pulsed autologous monocyte-derived mature dendritic cells with a fixed interval. The dendritic cells are generated from leukapheresis products and frozen after antigen loading.

HLA A2 positive patients are treated with PADRE and oncopeptide pulsed DC; survivin and telomerase peptides. HLA A2 negative patients are treated with KLH and tumorlysate pulsed DC; autologous or allogeneic. Each patient is given 6 immunizations with at least 5x106 peptide/lysate pulsed autologous DC. Vaccination 1-4 is given weekly and 4-6 at 2-week intervals. Those patients who exhibit stable disease, partial response or complete response after 6 injections will be given 4 more vaccinations at 2-week interval. The vaccine is applied by intradermal injection near the inguinal region. IL-2 2 MIU s.c. day 2-6 and Thymosin alpha 1 (Zadaxin®, SciClone) 1,6 mg s.c. twice a week are used for adjuvants. Scans and re-staging tests are performed at scheduled intervals throughout the study.

Eligibility criteria: Inclusion Criteria:

* Histologically proven progressive metastatic or locally advanced renal cell carcinoma
* No standard treatment indicated
* Age: \> 18
* WHO-Performance Status 0-1
* At least tone measurable tumor lesions according to the RECIST criteria.
* Life expectancy more than 3 months
* Acceptable CBC and blood chemistry results
* Written informed consent

Exclusion Criteria:

* Patients with a history of any other neoplastic disease less than 5 years ago (excepting treated carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin).
* Patients with metastatic disease in the central nervous system (CNS).
* Patients with other significant illness including severe allergy, asthma, angina pectoris or congestive heart failure.
* Patients with acute or chronic infection including HIV, hepatitis and tuberculosis.
* Patients who are pregnant.
* Patients who have received antineoplastic therapy including chemotherapy or immunotherapy less than 4 weeks before beginning the trial.
* Patients who receive corticosteroids or other immunosuppressive agents.
* Baseline serum LDH greater than 4 times the upper limit of normal.
* Patients with active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or thyroiditis.

Primary outcomes:
measure: Primary aim of the study is to evaluate tolerability and safety of the treatment.
timeFrame: weekly for the first four weeks, thereafter biweekly
Secondary outcomes:
measure: Secondary aims: evaluation of treatment induced immune response and clinical response.
timeFrame: after 8 and 16 weeks of treatment
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Department of Oncology, Copenhagen University Hospital, Herlev
Study officials:
affiliation: Department of Oncology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
name: Inge Marie Svane, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Svane IM, Pedersen AE, Johnsen HE, Nielsen D, Kamby C, Gaarsdal E, Nikolajsen K, Buus S, Claesson MH. Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study. Cancer Immunol Immunother. 2004 Jul;53(7):633-41. doi: 10.1007/s00262-003-0493-5. Epub 2004 Feb 25.