Clinical trial NCT00720031: Treatment of Metastatic Melanoma With Autologous Melan-A/MART-1 Specific CTL Clones
Official title: Treatment of Metastatic Melanoma With Autologous Melan-A/MART-1 Specific CTL Clones
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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.
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2008-07-22
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: one year
Secondary outcomes:
measure: 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
timeFrame: after treatment
measure: Evaluate whether infused T cell clones transfer a specific immunity.
timeFrame: J56 after treatment
measure: evaluate infused Melan-A/MART1 reactive T cell clones tolerance
timeFrame: one year
Other outcomes:
Locations:
city: Nantes
country: France
facility: Nantes University Hopspital
state: Pays de la Loire
Study officials:
affiliation: Nantes University Hospital
name: Brigitte DRENO, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.