Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE) (Protocol LUPSENIC) (LUPSENIC)
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE)|
- Cardiac adverse events whatever grade and any adverse event of grade 3 or 4 [ Time Frame: 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.
- Composite response of SLE [ Time Frame: 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-nuclear antibodies (ANA). [ Time Frame: 30 months ]The modification of anti-nuclear antibodies (ANA).
- Anti-native DNA [ Time Frame: 30 months ]The modification of anti-native DNA.
- C3 complement [ Time Frame: 30 monhs ]The modification of C3 complement.
- C4 complement [ Time Frame: 30 months ]The modification of C4 complement.
- Sedimentation rate [ Time Frame: 30 months ]Analysis of Sedimentation rate.
- Serum creatinine [ Time Frame: 30 months ]Analysis of serum creatinine.
- Proteinuria/creatinuria ratio [ Time Frame: 30 months ]Analysis of proteinuria/creatinuria ratio.
- Serum protein electrophoresis [ Time Frame: 30 months ]Analysis of serum protein electrophoresis.
- Quantitation of immunoglobulins [ Time Frame: 30 months ]Analysis of quantitation of immunoglobulins.
- Quality of life [ Time Frame: 30 months ]Assessment of quality of life wih questionnaires SF36 and LupusQol.
- Steroids [ Time Frame: 30 months ]Reduction of the dose of steroids throughout the study.
- Immunosuppressive treatments [ Time Frame: 30 months ]Cessation of immunosuppressive treatments.
- Response time [ Time Frame: 30 months ]Response time in case of positive response.
- Time to relapse [ Time Frame: 30 months ]Time to relapse in case of positive response.
- Blood test of arsenic [ Time Frame: 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.
|Study Start Date:||July 2013|
|Study Completion Date:||October 2015|
|Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: 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).
Drug: Arsenic trioxide
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 :
Please refer to this study by its ClinicalTrials.gov identifier: NCT01738360
|CHU de Bordeaux|
|CHRU de Lille|
|CHU de Marseille|
|Nantes University Hospital|
|Nantes, France, 44093|
|AP-HP - la Pitié-Salpétrière|
|CHRU de Strasbourg|
|Principal Investigator:||Mohamed HAMIDOU, Profesor||CHU de Nantes|
|Study Chair:||Zahir AMOURA, Profesor||AP-HP - La Pitié-Salpétrière|
|Study Chair:||Jean SIBILIA, Profesor||CHRU de Strasbourg|
|Study Chair:||Jean-François VIALLARD, Profesor||University Hospital, Bordeaux|
|Study Chair:||Nicolas SCHLEINITZ, Profesor||CHU de Marseille|
|Study Chair:||Eric HACHULLA, Profesor||CHRU de Lille|