Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE) (Protocol LUPSENIC)
- Registration Number
- NCT01738360
- Lead Sponsor
- Nantes University Hospital
- Brief Summary
Primary 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
- 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).
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arsenic trioxide Arsenic trioxide 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).
- Primary Outcome Measures
Name Time Method Cardiac adverse events whatever grade and any adverse event of grade 3 or 4 30 days after the last infusion The definition of toxicity will be based on "Common Terminology Criteria for Adverse Events, version 4" of the U.S. Department of Health and Human Services, National Institutes of Health / National Cancer Institute.
The investigators will consider the occurrence of a significant toxicity if at least one of the following events is observed :
* Any symptomatic toxicity (and / or abnormality) cardiac and / or QTc prolongation \> 480 msec.,
* Apart from cardiac toxicity, toxicity of any grade 3 or 4 and irreversible toxicity (within 30 days) of any grade 1 or 2.
- Secondary Outcome Measures
Name Time Method Composite response of SLE 30 months Combined clinical response using the composite response of SLE or SRI (SLE Responder Index) (SLEDAI + BILAG (British Isles Lupus Assessment Group) + PGA) : a positive response is defined by a reduction of SELENA SLEDAI of at least 4 points, no worsening ( \> 0,3 point) of the physician's global assessment (PGA), no new score "A" and no more than one new score "B" about BILAG. This composite index is now the benchmark tool for evaluating therapeutic protocols in SLE.
Anti-native DNA 30 months The modification of anti-native DNA.
Anti-nuclear antibodies (ANA). 30 months The modification of anti-nuclear antibodies (ANA).
C4 complement 30 months The modification of C4 complement.
Sedimentation rate 30 months Analysis of Sedimentation rate.
Serum creatinine 30 months Analysis of serum creatinine.
Proteinuria/creatinuria ratio 30 months Analysis of proteinuria/creatinuria ratio.
Quantitation of immunoglobulins 30 months Analysis of quantitation of immunoglobulins.
Quality of life 30 months Assessment of quality of life wih questionnaires SF36 and LupusQol.
Steroids 30 months Reduction of the dose of steroids throughout the study.
Immunosuppressive treatments 30 months Cessation of immunosuppressive treatments.
C3 complement 30 monhs The modification of C3 complement.
Response time 30 months Response time in case of positive response.
Time to relapse 30 months Time to relapse in case of positive response.
Blood test of arsenic D1, D2, D3, D4, D8, D11, D15, D18, D22 and D25 (before and after each infusion) Pharmacokinetic study of arsenic plasma with analysis of potential correlations blood rates/ toxicity and response.
Serum protein electrophoresis 30 months Analysis of serum protein electrophoresis.
Trial Locations
- Locations (6)
CHU de Marseille
🇫🇷Marseille, France
Nantes University Hospital
🇫🇷Nantes, France
CHRU de Strasbourg
🇫🇷Strasbourg, France
CHRU de Lille
🇫🇷Lille, France
AP-HP - la Pitié-Salpétrière
🇫🇷Paris, France
CHU de Bordeaux
🇫🇷Bordeaux, France