Immunotherapy
Conditions
Keywords
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.
Brief summary
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.
Interventions
BIOLOGICALautologous 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.
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
France
Outcome results
None listed