Adoptive Cell Transfer Combined With Peptide Vaccination in Transiently Immunosuppressed Melanoma Patients

Study Overview
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Brief Summary
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Patients with advanced stage melanoma who underwent vaccination with the Melan-A/MART-1 peptide and who display detectable levels of Melan-A specific CD8+ T cells in peripheral blood are eligible for this trial. After collecting and freezing of these tumor specific T cells via apheresis, patients undergo a single cycle of immunosuppressive chemotherapy. 3 days after, cells are reinfused and peptide vaccination continued. The aim of this immunotherapy protocol is to boost tumor specific T cells during the immune recovery period in order to reinforce the patients' immune response against the tumor.

Detailed Description
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Patients who have previously been vaccinated with Melan-A/MART-1 peptide are eligible. Whole PBMC's containing Melan-A specific CD8+ lymphocytes are collected via lymphocytapheresis and freezed. Lymphodepleting chemotherapy consists of 2 days of Busulfan 2mg/kg at days -7,-6, followed by Fludarabine 30mg/m2 at days -5,-4,-3. At day 0, whole untreated PBMC's are reinfused to the patient and vaccination with Melan-A analog peptide is restarted and repeated every 4 weeks. Immunomonitoring with detailed FACS analysis using tetramers is performed at day 0,8,15,30, and then monthly. The aim is to boost Melan-A specific CD8 T cells in vivo during homeostatic proliferation after lymphodepletion and antigen driven proliferation due to peptide vaccination.

Official Title
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Phase I Study of in Vivo Expansion of Melan-A/MART-1 Antigen-Specific CD8 T Lymphocytes Following Transient Immunosuppression in Patients With Advanced Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Biological: Melan-A analog peptide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IV melanoma tumor expressing Melan-A patient of HLA-A2 subtype Detectable immune response after peptide vaccination with Melan-A Disease progression during peptide vaccination Exclusion Criteria: Cerebral metastases rapidly progressive disease, that necessitates systemic chemotherapy

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

| Intervention/Treatment |
| --- |
|Biological: Melan-A analog peptide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity and feasibility |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunomonitoring of the immune reconstitution period |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adoptive cell transfer, peptide vaccination, melanoma, immunosuppression and homeostatic proliferation