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

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

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).

Study Overview

• Status: Completed
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Biological: Melanoma antigens-specific CD8+ T lymphocytes

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44000
    • Nantes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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")

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	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
Overall survival	From the date of the first treatment until the date of death, assessed up to 2 years
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)	At 12 months
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	At 12 months
Persistence of injected specific T cells evaluated by immunomonitoring	At 3 months

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: UMR892

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2015
• Primary Completion (Actual): May 6, 2019
• Study Completion (Actual): May 6, 2019

Study Registration Dates

• First Submitted: April 3, 2015
• First Submitted That Met QC Criteria: April 22, 2015
• First Posted (Estimate): April 23, 2015

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 15, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Immunotherapy; Onco-dermatology; Adoptive transfer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: RC12_0261

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No