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

Sponsor:	Nantes University Hospital
Information provided by:	Nantes University Hospital
ClinicalTrials.gov Identifier:	NCT00720031

Purpose

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	Intervention	Phase
Immunotherapy	Biological: autologous Melan-A/MART-1 specific CTL clones	Phase I Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Treatment of Metastatic Melanoma With Autologous Melan-A/MART-1 Specific CTL Clones

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

U.S. FDA Resources

Further study details as provided by Nantes University Hospital:

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 [ Time Frame: one year ] [ Designated as safety issue: No ]

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 [ Time Frame: after treatment ] [ Designated as safety issue: No ]
Evaluate whether infused T cell clones transfer a specific immunity. [ Time Frame: J56 after treatment ] [ Designated as safety issue: No ]
evaluate infused Melan-A/MART1 reactive T cell clones tolerance [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment:	16
Study Start Date:	November 2000
Study Completion Date:	May 2008
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Intervention Details:

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720031

Locations

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

Sponsors and Collaborators

Nantes University Hospital

Investigators

Principal Investigator:

Brigitte DRENO, PhD

Nantes University Hospital

More Information

No publications provided

Responsible Party:	general director, Nantes University Hospital
ClinicalTrials.gov Identifier:	NCT00720031 History of Changes
Other Study ID Numbers:	BRD 98/9-C
Study First Received:	July 18, 2008
Last Updated:	July 22, 2008
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Nantes University Hospital:

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.

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on February 09, 2012