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

Sponsor

Nantes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00720031

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Immunotherapy	Biological: autologous Melan-A/MART-1 specific CTL clones	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2000

Actual Primary Completion Date :

May 1, 2008

Actual Study Completion Date :

May 1, 2008

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.