Autologous EBV-specific Cytotoxic T Cells for the Treatment of Systemic Lupus Erythematosus (SLE)

Phase 1

Terminated

• Conditions: Serologically Active Adult Systemic Lupus Erythematosus
• Interventions: Biological: Autologous EBV specific CTL infusion

• Registration Number: NCT02677688
• Lead Sponsor: Nantes University Hospital

Brief Summary

EBV has been implicated in pathogeny of SLE with increase in EBV sero-prevalence, defective control in EBV infection and altered both B and T immune responses to this virus The main objective of this pilot proof-of-concept (POC) study is to evaluate safety and efficacy of autologous EBV specific CTL adoptive transfer in adult patients with serologically active SLE

Detailed Description

Systemic lupus is a disabling disease of the young woman, whose treatment is based on the long-term corticosteroid, anti-malarials and immunosuppressants synthesis. This support is not without potential side effects. EBV is a herpes causes infectious mononucleosis virus, usually encounter in childhood or adolescence, and that our natural immunity cell (CD8 T cells) controls all our lives, not eliminate.

Increasingly scientific studies show that there are patients with systemic lupus (and multiple sclerosis), a failure of self-control of the EBV virus, by T lymphocytes (CD8). This uncontrolled virus then stimulate the B lymphocytes, which produce antibodies, toxic in lupus. The laboratory isolate T cells specific for EBV (EBV-CTL) of a patient, and stimulate in culture to strengthen them. They can be then re-injected by a single intravenous infusion (autotransfusion), and were used to control the virus in certain diseases where EBV has a demonstrated role post-transplant lymphoproliferative disorder, chronic fatigue syndrome EBV-induced.

Our therapeutic approach is completely innovative, as based on the principle of cell therapy, thus not using new drugs, and based on the restoration of the patient's immune system, specific EBV.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-28
• Study First Submitted QC: 2016-02-04
• Study First Posted: 2016-02-09
• Primary Completion: 2021-07-01
• Study Completion: 2021-07-01
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-24
• Last Update Posted: 2022-03-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

• 4 systemic lupus criteria of the American College of Rheumatology with antinuclear antibodies> 1:80
• Age greater than or equal to 18 years
• Lupus serologically active without active serious disease (Kidney, CNS)
• Anti-native DNA Ac positive and / or C3 or C4 low
• SLEDAI greater than or equal to 2 at baseline
• Serology HBV, HCV, HIV, HTLV-1, syphilis: Negative J-30 before sample
• Hemoglobin >11g/dL
• Prednisone dose <15 mg / day with a stable dose within 30 days previous injection
• Immunosuppressive treatments which dosage has not been increased for at least 3 months before enrollment
• Agreement telephone and / or mail for coordinating investigator inclusion
• Social ensured Patient
• EBV positive serology

Exclusion Criteria

• Evolving severe lupus, requiring high dose corticosteroids and / or immunosuppressive therapy
• Psychiatric disorders
• Predicted Failure to monitoring compliance with impossibility
• Infectious Episode underway
• Evolutionary Cancer
• Risk of death within 6 months
• Consent Refusal
• Pregnancy
• Nursing women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Autologous EBV specific CTL infusion	Autologous EBV specific CTL infusion	-

Primary Outcome Measures

Name	Time	Method
description of adverse events according CTC toxicity criteria .	month 12	Tolerance will be assessed by clinical and laboratory examinations to each Visit according to CTC toxicity criteria.

Secondary Outcome Measures

Name	Time	Method
Lupus Quality of Life	day 0, day 10, week 4, month 3, month 6, month 9 and month 12	Lupus Quality of Life questionnaire
Systemic Lupus Erythematosus biological activity (2)	day 0, day 10, week 4, month 3, month 6, month 9 and month 12	biological parameter measurement biomarkers C4
Systemic Lupus Erythematosus biological activity (1)	day 0, day 10, week 4, month 3, month 6, month 9 and month 12	biological parameter measurement biomarkers C3
Systemic Lupus Erythematosus biological activity (4)	day 0, day 10, week 4, month 3, month 6, month 9 and month 12	biological parameter EBV blood load
Quality of Life, The Short Form (36) Health Survey	day 0, day 10, week 4, month 3, month 6, month 9 and month 12	The Short Form (36) Health Survey
Systemic Lupus Erythematosus biological activity (3)	day 0, day 10, week 4, month 3, month 6, month 9 and month 12	biological parameter measurement biomarkers anti-dsDNA antibodies
Systemic Lupus Erythematosus clinical activity	day 0, day 10, week 4, month 3, month 6, month 9 and month 12	Composite Response of SLE Index (Systemic Lupus Erythematosus Responder Index: Systemic Lupus Erythematosus Disease Activity Index + British Isles Lupus Assessment Group + Physician Global Assessment)

Trial Locations

Locations (3)

CHU de Nantes - Dermatologie; 🇫🇷 Nantes, France

Hopital La pitié Salpétriere; 🇫🇷 Paris, France

CHU de Nantes - Médecine interne; 🇫🇷 Nantes, France