Treatment of Metastatic Melanoma With Autologous Melan-A/MART-1 Specific CTL Clones

Study Overview
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Brief Summary
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Most of HLA-A2 melanomas express Melan-A/MART-1 antigen and are recognized by tumor reactive Melan-A specific T lymphocytes. By using blood samples from HLA-A2 melanoma patients (stage III and IV), our goal is to produce a tumor reactive Melan-A specific T cell clones and to conduct a phase I-II clinical trial, based on the infusion of several millions to several billions of these lymphocytes to the patient, in order to induce passive immunity against this antigen. Production of the clones will be performed in the Unit for Cellular and Gene Therapy from Nantes University Hospital. Therapeutic response, safety treatment but also localization and survival of infused T cell clones will be assessed. This approach is expected to precise the ability of the clones to migrate within the tumor and to transfer specific immunity.

Official Title
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Treatment of Metastatic Melanoma With Autologous Melan-A/MART-1 Specific CTL Clones

Conditions
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Immunotherapy

Intervention / Treatment
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* Biological: autologous Melan-A/MART-1 specific CTL clones


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HLA-A2 melanoma patients with : either loco-regional or lymph node metastasis transit nodules not surgically resectable measurable cutaneous or visceral metastasis Patients' tumor express Melan-A/MART-1 antigen. No chemotherapy treatment (except for Deticene used before the first T cell clones infusion) or radiotherapy or immunotherapy in the last 4 weeks before infusion. No other melanoma treatment during the protocol. Life expectancy should be greater than 6 months. General state with Karnowsky greater than 80, ECOG = 0, 1 or 2. Patient should be negative for HIV and B and C hepatitis. Biological parameters at the beginning of the study: leucocytes ³ 2000 elements per mm3, hemoglobin ³ 10.5g/dl, platelets ³ 100 000 per mm3, phosphatases alcalines transaminases £ 1 time 1/2 compared to the normal. Signed informed consent Exclusion Criteria: Cardio-vascular pathologies, evoluting and uncontrolled, (severe HTA), cardiac deficiency, severe angor, severe arrhythmia. Infectious pathologies evoluting and requiring antibiotherapy. Patients HIV+. Transplanted patients or patients suffering from severe auto-immune disease. Psychiatric troubles that do not allow the protocol follow-up. Pregnant or breast-feeding women. No contraception.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: autologous Melan-A/MART-1 specific CTL clones|By using patients' blood, several million to several billion of Melan-A/MART1 tumor reactive T cell clone(s) will be produced in vitro, then infused to the patient, 3 to 6 months after collecting blood sample. During this production period of the T cell clone, the patient will be treated with deticene at the dose of 250mg/m2/j by IV for 4 days each month. After each T cell clone infusion (J1), the patient will receive IFN-α at the dose of 9 M/U 3 times a week for 4 weeks and Interleukin-2 at the dose of 9 M/U from Day 1 to day 5 and from Day 8 to Day 12.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of an adoptive immunotherapy specific for Melan-A/MART1 antigen in metastatic melanoma patients whose tumor express this antigen but also HLA-A2 |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate whether infused T cell clones migrate to tumor sites. For this purpose, infused T cell clones will be characterized according to their Vß and Valpha using antibodies and/or PCR |  | after treatment | 
| Evaluate whether infused T cell clones transfer a specific immunity. |  | J56 after treatment | 
| evaluate infused Melan-A/MART1 reactive T cell clones tolerance |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma,, Melan-A tumor reactive T cell clones,, immunotherapy, HLA-A2 melanoma patients with, either loco-regional or lymphnode metastasis, transit nodules not surgically resectable, -measurable cutaneous or visceral metastasis ., Patients' tumor express Melan-A/MART-1 antigen.