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

Primary Purpose

Immunotherapy

Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
autologous Melan-A/MART-1 specific CTL clones
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Immunotherapy focused on measuring 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.

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Nantes University Hopspital

Outcomes

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

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
Evaluate whether infused T cell clones transfer a specific immunity.
evaluate infused Melan-A/MART1 reactive T cell clones tolerance

Full Information

First Posted
July 18, 2008
Last Updated
July 22, 2008
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00720031
Brief Title
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

2. Study Status

Record Verification Date
July 2008
Overall Recruitment Status
Completed
Study Start Date
November 2000 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Nantes University Hospital

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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.

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
autologous Melan-A/MART-1 specific CTL clones
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
Evaluate whether infused T cell clones transfer a specific immunity.
Time Frame
J56 after treatment
Title
evaluate infused Melan-A/MART1 reactive T cell clones tolerance
Time Frame
one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brigitte DRENO, PhD
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nantes University Hopspital
City
Nantes
State/Province
Pays de la Loire
ZIP/Postal Code
44093
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
25846669
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.
Results Reference
derived

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

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