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

Restauration of EBV Control in SLE Phase 1-2 Trial Evaluating Adoptive Transfer of Autologous EBV- Specific Cytotoxic T Lymphocytes in SLE Treatment

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

Study Overview

• Status: Terminated
• Conditions: Serologically Active Adult Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: Autologous EBV specific CTL infusion

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Nantes, France
    • CHU de Nantes - Dermatologie
  • Nantes, France
    • CHU de Nantes - Médecine interne
  • Paris, France
    • Hôpital La Pitié Salpêtrière

Participation Criteria

Eligibility Criteria

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

Description

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 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 EBV specific CTL infusion	Biological: Autologous EBV specific CTL infusion

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Study Director: Mohamed Hamidou, PU PH, CHU de Nantes

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: January 28, 2016
• First Submitted That Met QC Criteria: February 4, 2016
• First Posted (Estimate): February 9, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: systemic lupus erythematosus; autologous anti-EBV CTL; adoptive therapy; phase 1 -2
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: BRD/10/06-X

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No