Phase 2a Study Evaluating the Arsenic Trioxide (ATO) in Systemic Lupus (SLE) (Protocol LUPSENIC)

Nantes University Hospital (NUH)

Status and phase: Terminated; Phase 2

Conditions: Systemic Lupus

Treatments: Drug: Arsenic trioxide

Study type: Interventional

Funder types: Other

Identifiers

NCT01738360

2012-002259-40 (EudraCT Number)

RC12_0021

Details and patient eligibility

About

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.

Enrollment: 11 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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11 participants in 1 patient group

Arsenic trioxide

Experimental group

Description:

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).

Treatment:

Drug: Arsenic trioxide