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

Metastatic Melanoma Clinical Trial

— MelSort  

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 Details — Status: Completed

Administrative data

• NCT number: NCT02424916
• Other study ID #: RC12_0261
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 26, 2015
• Est. completion date: May 6, 2019

Study information

• Verified date: January 2020
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: May 6, 2019
• Est. primary completion date: May 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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")

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

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.

Locations

Country	Name	City	State
France	Nantes University Hospital	Nantes

Sponsors (2)

Lead Sponsor	Collaborator
Nantes University Hospital	UMR892

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall survival		From the date of the first treatment until the date of death, assessed up to 2 years
Secondary	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
Secondary	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
Secondary	Persistence of injected specific T cells evaluated by immunomonitoring		At 3 months