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

NCT02424916 | Completed Phase 1 DMC

• 1 other identifier: RC12_0261
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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).

Conditions

Metastatic Melanoma

Keywords

Onco-dermatology; Adoptive transfer; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (1)

Autologous somatic cell therapy

EXPERIMENTAL

Patients treated with melanoma antigens-specific CD8+ T lymphocytes followed by subcutaneous injections of Proleukin.

Biological: Melanoma antigens-specific CD8+ T lymphocytes

Interventions

Melanoma antigens-specific CD8+ T lymphocytes BIOLOGICAL

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.

Autologous somatic cell therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Brain metastases
• Ocular primitive melanoma
• 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")

Sponsors & Collaborators

• Nantes University Hospital: lead
• UMR892: collaborator

Study Sites (1)

Nantes University Hospital

Nantes, 44000, France

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2015
• First Posted: April 23, 2015
• Study Start: May 26, 2015
• Primary Completion: May 6, 2019
• Study Completion: May 6, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

FR (1)