Phase II Study With Immunotherapy With Dendritic Cells and Tumor Infiltrating Lymphocytes in Solid Tumors

Study Overview
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Brief Summary
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Background: cellular immunotherapy with dendritic cells (DC) loaded with tumor antigens has shown clinical activity, although in a small number of patients. Therefore, is is mandatory to improve the results of this strategy and to closely monitor immunologic response and cell migration in order to improve our understanding of mechanisms of action and to settle future fields of development.. Objectives: Primary: to confirm clinical activity of this strategy, determining tumor response (RECIST criteria). Secondary: to determine: (1) safety; (2) antitumoral immune response and (3) DC migration in the organism Methodology: phase II trial in patients with advanced renal cell carcinoma and melanoma. We will perform repeated immunizations with DC loaded with the patient´s tumor.

Detailed Description
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Background: cellular immunotherapy with dendritic cells (DC) loaded with tumor antigens has shown clinical activity, although in a small number of patients. Therefore, is is mandatory to improve the results of this strategy and to closely monitor immunologic response and cell migration in order to improve our understanding of mechanisms of action and to settle future fields of development.. Objectives: Primary: to confirm clinical activity of this strategy, determining tumor response (RECIST criteria). Secondary: to determine: (1) safety; (2) antitumoral immune response (through study of delayed hypersensitivity; ELISPOT; activity of Natural Killer cells; and serum cytokine concentrations); and (3) DC migration in the organism, by labeling with 111-Indium oxinate Methodology: phase II trial in patients with advanced renal cell carcinoma and melanoma. We will perform repeated immunizations with mature DC loaded with autologous tumor. We will introduce the following novel elements to enhance efficacy (1) Pre-treatment with cyclophosphamide to reduce regulatory / suppressor T cells; (2) maturation/activation of DC induced by TNF-alfa, IFN-alfa and double stranded RNA (GMP-manufactured poly I:C), aimed at replication of the phenomena observed during a viral infection (3) intranodal DC administration in inguinal lymph nodes (4) four daily doses (repeated every 24 hours) in two cycles one month apart (5) scintigraphic follow-up of a tracing dose of 111-In labelled DC and (6) ) systemic treatment with PEG-IFN alfa and GM-CSF to potentiate activity.

Official Title
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Phase II Study With Immunotherapy With Dendritic Cells and Tumor Infiltrating Lymphocytes in Solid Tumors

Conditions
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Renal Cell Carcinoma, Melanoma, Carcinoma, Hepatocellular

Intervention / Treatment
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* Biological: immunotherapy with dendritic cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of metastatic melanoma, renal cell carcinoma, or hepatocarcinoma (Child´s stage A or B) not amenable of curative treatment. For patients with hepatocarcinoma, treatment after embolization is allowed Measurable disease ECOG 0, 1 or 2. Adequate renal, hepatic and bone marrow function Availability of tumor tissue, for maturing dendritic cells Exclusion Criteria: Clinically relevant diseases or infections. concurrent participation in other clinical trial or administration or other antitumoral treatment Concurrent cancer, with the exceptions allowed by the PI. Pregnant or breast feeding women immunosuppressant treatment known CNS metastasis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: immunotherapy with dendritic cells<br>* We will administer four daily doses (repeated every 24 hours)o dendritic cells in two cycles one month apart. We will administer systemic treatment with PEG-IFN alfa and GM-CSF to potentiate activity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological response |  | 2 months |