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

NCT00720031 | Completed Phase 1

• 1 other identifier: BRD 98/9-C
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Immunotherapy

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.

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Interventions

autologous Melan-A/MART-1 specific CTL clones BIOLOGICAL

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

Nantes University Hopspital

Nantes, Pays de la Loire Region, 44093, France

Location

Related Publications (1)

• 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.

  PMID: 25846669 DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Brigitte DRENO, PhD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 18, 2008
• First Posted: July 22, 2008
• Study Start: November 1, 2000
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: July 24, 2008

Record last verified: 2008-07

Locations

FR (1)