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Adoptive Transfer of Specific Melanoma Antigens CD8+ T Cells in Metastatic Melanoma Patients: a Phase I/II Study

NCT02424916

Description:

This study evaluates the safety as well as the potential clinical efficacy of an adoptive transfer of CD8+ T cells, sorted with HLA-peptide multimers and specific for Melan-A and MELOE-1 melanoma antigens, to patients suffering from advanced metastatic melanoma (stages IIIc and IV).

Related Conditions:
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adoptive Transfer of Specific Melanoma Antigens CD8+ T Cells in Metastatic Melanoma Patients: a Phase I/II Study
  • Official Title: Adoptive Transfer of CD8+ T Cells, Sorted With HLA-peptide Multimers and Specific for Melan-A and MELOE-1 Melanoma Antigens, to Metastatic Melanoma Patients. A Phase I/II, Non-randomized, Open Monocentric Study

Clinical Trial IDs

  • ORG STUDY ID: RC12_0261
  • NCT ID: NCT02424916

Conditions

  • Metastatic Melanoma

Interventions

DrugSynonymsArms
Melanoma antigens-specific CD8+ T lymphocytesAutologous somatic cell therapy

Purpose

This study evaluates the safety as well as the potential clinical efficacy of an adoptive transfer of CD8+ T cells, sorted with HLA-peptide multimers and specific for Melan-A and MELOE-1 melanoma antigens, to patients suffering from advanced metastatic melanoma (stages IIIc and IV).

Trial Arms

NameTypeDescriptionInterventions
Autologous somatic cell therapyExperimentalPatients treated with melanoma antigens-specific CD8+ T lymphocytes followed by subcutaneous injections of Proleukin.
  • Melanoma antigens-specific CD8+ T lymphocytes

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female ≥ 18 and ≤ 75 years

          -  Patient expressing the HLA-A*0201 subtype of the human leukocyte antigen (HLA -A2)

          -  Patient with metastatic melanoma stage IIIc or IV (AJCC 2010) except brain metastases

          -  Tumor expressing the antigens Melan-A and MELOE-1 detected by RT-PCR

          -  Absence of cerebral metastases

          -  ECOG ≤ 1 or Karnofsky ≥ 80%

          -  Prior adjuvant melanoma treatment (before metastatic stage) authorized (anti- BRAF,
             anti-CTLA4, IFN, TIL... )

          -  Disease measurable / evaluable within 28 days before the first administration of study
             treatment

          -  Negative viral serology (HIV 1/2, Ag p24 , HTLV 1/2 , hepatitis B and C, syphilis)

          -  Results of analysis:

               -  Hemoglobin ≥ 10 g / dl or ≥ 6.25 mmol / l

               -  Leukocytes ≥ 4000/μl

               -  Lymphocytes ≥ 1500/μl

               -  Platelets ≥ 80.000/μl

               -  Creatinine ≤ 2.5 N

               -  Total bilirubin ≤ 3 N

               -  AST and ALT ≤ 3 N without liver metastases; ≤ 5 N with liver metastases

          -  Negative pregnancy test for women of childbearing age

          -  Patient affiliated to a social security system

          -  Patient who has signed informed consent

        Exclusion Criteria:

          -  Brain metastases

          -  Ocular primitive melanoma

          -  Treatment of metastatic melanoma by more than two lines (chemotherapy , immunotherapy,
             targeted therapy or radiotherapy) or within 4 weeks before the inclusion

          -  Treatment with ipilimumab within 8 weeks before the inclusion

          -  Known allergy to albumin

          -  Contraindication to the use of vasopressors

          -  Positive viral serology for HIV 1/2 , Ag p24 , HTLV 1/2, hepatitis B or C, or syphilis

          -  Women who are pregnant, nursing or refusing to use contraceptives, women with no
             negative pregnancy test at baseline

          -  Presence of a second active cancer (with the exception of cervical cancer in situ or
             skin cancer other than melanoma)

          -  History of event or current event of a progressive or non-stabilized severe heart
             disease (congestive heart failure, coronary artery disease, uncontrolled hypertension,
             serious arrhythmias or ECG signs of previous myocardial infarction)

          -  Uncontrolled thyroid dysfunction

          -  Any serious acute or chronic illness (active infection requiring antibiotics, bleeding
             disorders or other condition requiring concomitant treatment not allowed in this
             study)

          -  History of chronic autoimmune disease (Addison's disease, multiple sclerosis, Graves'
             disease, rheumatoid arthritis, systemic lupus erythematosus, ... ) with the exception
             of patients with active vitiligo or a history of vitiligo

          -  History of uveitis and retinopathy associated with melanoma

          -  Adults under a legal protection regime (guardianship, trusteeship, "sauvegarde de
             justice")
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical and biological safety defined by the NCI (Common Toxicity Criteria - Version 4.0, may 2009, http:// ctep.cancer.gov)
Time Frame:Until disease progression during the follow-up period of the study (12 months)
Safety Issue:
Description:Serious adverse effects of grade 3 and 4 will be considered to decide the suspension of inclusion

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:From the date of the first treatment until the date of the first documented progression or the date of death from any cause, whichever came first, assessed up to 2 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:From the date of the first treatment until the date of death, assessed up to 2 years
Safety Issue:
Description:
Measure:Overall tumor response (complete response, partial response, stable disease) evaluated according to Response Evaluation Criteria in Solid Tumor (RECIST) and immune-related Response Criteria (irRC)
Time Frame:At 12 months
Safety Issue:
Description:
Measure:Duration of clinical responses defined as the time interval between the evaluation of the first objective response or stable disease and the first evaluation of disease progression
Time Frame:At 12 months
Safety Issue:
Description:
Measure:Persistence of injected specific T cells evaluated by immunomonitoring
Time Frame:At 3 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nantes University Hospital

Trial Keywords

  • Onco-dermatology
  • Adoptive transfer
  • Immunotherapy

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