Metastatic Melanoma
Conditions
Keywords
Onco-dermatology, Adoptive transfer, Immunotherapy
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).
Interventions
BIOLOGICALMelanoma 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.
Sponsors
UMR892
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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 ≤ 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical and biological safety defined by the NCI (Common Toxicity Criteria - Version 4.0, may 2009, http:// ctep.cancer.gov) | 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
| 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 |
Countries
France
Outcome results
None listed