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

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.

Study Overview

• Status: Completed
• Conditions: Immunotherapy
• Intervention / Treatment: Biological: autologous Melan-A/MART-1 specific CTL clones

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Pays de la Loire
    • Nantes, Pays de la Loire, France, 44093
      • Nantes University Hopspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Brigitte DRENO, PhD, Nantes University Hospital

Publications and helpful links

General Publications

• Khammari A, Nguyen JM, Saint-Jean M, Knol AC, Pandolfino MC, Quereux G, Brocard A, Peuvrel L, Saiagh S, Bataille V, Limacher JM, Dreno B. Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-gamma) in metastatic melanoma patients. Cancer Immunol Immunother. 2015 Jul;64(7):805-15. doi: 10.1007/s00262-015-1691-7. Epub 2015 Apr 7.

Study record dates

Study Major Dates

• Study Start: November 1, 2000
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: July 18, 2008
• First Submitted That Met QC Criteria: July 21, 2008
• First Posted (Estimate): July 22, 2008

Study Record Updates

• Last Update Posted (Estimate): July 24, 2008
• Last Update Submitted That Met QC Criteria: July 22, 2008
• Last Verified: July 1, 2008

More Information

Terms related to this study

• Keywords: immunotherapy; Melanoma,; Melan-A tumor reactive T cell clones,; 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.
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: BRD 98/9-C