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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02424916
Recruitment Status : Recruiting
First Posted : April 23, 2015
Last Update Posted : June 29, 2017
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Biological: Melanoma antigens-specific CD8+ T lymphocytes Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 26, 2015
Estimated Primary Completion Date : May 26, 2020
Estimated Study Completion Date : May 26, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Autologous somatic cell therapy
Patients treated with melanoma antigens-specific CD8+ T lymphocytes followed by subcutaneous injections of Proleukin.
Biological: Melanoma antigens-specific CD8+ T lymphocytes
The intervention uses an autologous somatic cell therapy medicinal product. It consists in the intravenous injection of melanoma antigens (Melan-A and MELOE-1) - specific CD8+ T lymphocytes followed by subcutaneous injections of Proleukin.

Primary Outcome Measures :
  1. Clinical and biological safety defined by the NCI (Common Toxicity Criteria - Version 4.0, may 2009, http:// [ Time Frame: Until disease progression during the follow-up period of the study (12 months) ]
    Serious adverse effects of grade 3 and 4 will be considered to decide the suspension of inclusion

Secondary Outcome Measures :
  1. 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 ]
  2. Overall survival [ Time Frame: From the date of the first treatment until the date of death, assessed up to 2 years ]
  3. 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 ]
  4. 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 ]
  5. Persistence of injected specific T cells evaluated by immunomonitoring [ Time Frame: At 3 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 ≤ 2 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")

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02424916

Contact: Brigitte Dréno, MD, PhD
Contact: Nathalie Labarrière, PhD

Nantes University Hospital Recruiting
Nantes, France, 44000
Contact: Amir Khammari, PhD   
Principal Investigator: Brigitte Dréno, MD, PhD         
Sponsors and Collaborators
Nantes University Hospital

Responsible Party: Nantes University Hospital Identifier: NCT02424916     History of Changes
Other Study ID Numbers: RC12_0261
First Posted: April 23, 2015    Key Record Dates
Last Update Posted: June 29, 2017
Last Verified: June 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nantes University Hospital:
Adoptive transfer

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas