Title
Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE) (Protocol LUPSENIC)
Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE)
Phase
Phase 2Lead Sponsor
University of NantesStudy Type
InterventionalStatus
TerminatedIndication/Condition
Systemic LupusIntervention/Treatment
arsenic trioxide ...Study Participants
11Primary objectives :
To investigate the safety and the tolerability of ATO by IV infusions to patients with SLE,
To determine the maximum tolerated dose of ATO.
Secondary objectives :
Evaluation of the clinical and biological response of the SLE to ATO,
Time of relapse in case of positive response,
Determination of the efficacy,
Pharmacokinetic study of ATO.
The study duration was 30 months (24 months recruitment + 6 months follow-up).Thirteen patients will be successively included in this study at 6 different dose levels of arsenic trioxide (0.075, 0.10, 015, 0.20, 0.25 and 0.30 mg / kg / day). The treatment should be administered by IV infusion over 2 hours of D1 to D4 (conventional hospitalization) and at D8, D11, D15, D18, D22 and D25. The protocol starts at the dose of 0.10 mg / kg / day. The stage at the dose of 0.075mg/kg/day is planned in case of toxicity with the first stage at the dose of 0.10mg/kg/day. The course of study is as follows : Pre-inclusion between D-35 and D-15 Ten injections during the first month distributed as follows : conventional hospitalization from D1 to D4 (one injection per day) and daily hospitalization day for injections at D8, D11, D15, D18, D22 and D25. A telephone contact between D32 and D34 A consultation at D40 then monthly consultation at D60, D90, D120, D150 and D180
Thirteen patients will be successively included in this study at 6 different dose levels of arsenic trioxide (0.075, 0.10, 015, 0.20, 0.25 and 0.30 mg / kg / day).
Inclusion Criteria: Systemic Lupus meeting the ACR (American College of Rheumatology) criteria, progressive either SLEDAI activity score ≥ 4, despite a corticosteroid therapy ≥ 10 mg / d associated with hydroxychloroquine (in the absence of contraindication or intolerance) and / or an immunosuppressive treatment at a stable dose, Insured, Availability for hospitalization required by the protocol (conventional and daily hospitalizations). Exclusion Criteria: Inability to give their signed informed consent form, Performans status > 2 QTcorrected space before treatment > 0.45 seconds Hemoglobin less than 11g/dL Neutrophils rate below 1 200 / mm3 Platelets rate below 100 Giga / mm3 Previous history of arrhythmia or heart rhythm disorder or other rhythm trouble by referring cardiologist Heart disorder (progressive pericarditis, valvular disease, ...) according to cardiologist Family previous history of arrhythmias Taking drugs that potentially prolong the QT Hypersensitivity to the active substance of Trisenox® or any of the excipients Serum potassium ≤ 4 milliequivalent / L Magnesemia ≤ 1,8 mg / dl Increase corticosteroids beyond 20 mg / day within 15 days before inclusion Immunosuppressive treatments, thalidomide introduced within the last 3 months Biotherapy (rituximab, belimumab, ...) introduced within 6 months prior to inclusion Pregnancy or lactation For women of childbearing age, men and their partner : unless effective contraception for the duration of participation in the study that is 7 months Creatinine clearance <50 ml / min, Hepatocellular insufficiency (TP <50%), and / or AST (aspartate aminotransferase) / ALT (alanine aminotransferase) / ALP (alkaline phosphatase) > 2N HBsAg positive, DNA detectable HbS Infection with HIV, HBV (hepatitis B virus) or HCV (hepatitis C virus) Renal or progressive central neurological impairment with possible alternative therapeutic (to be discussed with the principal investigator and scientific board meeting) Peripheral neuropathy Unweaned alcoholism Minor Patients older than 65 years Patient having been professionally exposed to arsenic (cleaning electronic circuits for example) Guardianship patients
