Serologically Active Adult Systemic Lupus Erythematosus
Conditions
Keywords
systemic lupus erythematosus, autologous anti-EBV CTL, adoptive therapy, phase 1 -2
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.
Interventions
BIOLOGICALAutologous EBV specific CTL infusion
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 (1) | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | biological parameter measurement biomarkers C3 |
| 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) |
| 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 biological activity (4) | day 0, day 10, week 4, month 3, month 6, month 9 and month 12 | biological parameter EBV blood load |
| 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 |
Countries
France
Outcome results
None listed