Brief Title
Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis
Official Title
MAINtenance of Remission Using RITuximab in Systemic ANCA-associated Vasculitis II
Brief Summary
The aim of this study is to assess the efficacy of a rituximab regimen based on rate of ANCA
and CD19 lymphocytes for maintenance treatment in systemic ANCA-associated vasculitis:
prospective, multicenter, controlled, randomized comparative study of two rituximab regimens:
one based on ANCA and CD19 lymphocytes versus systematic infusions.
Detailed Description
Randomized, controlled, national, multicenter, prospective study to compare systematic
rituximab infusions (conventional therapy) to rituximab infusion based on rate of ANCA and
CD19 lymphocytes in patients with systemic ANCA-associated vasculitis, in remission (achieved
with an induction treatment combining corticosteroids and an immunosuppressant after the
first flare of the disease (new diagnosis) or after a relapse. Patients will be stratified by
first flare (66% of the patients) or relapse (33% of the patients). Patients complying with
the inclusion criteria may be included when they are in remission from their vasculitis.
Patients will be included at the time of remission and then randomized. They will receive
maintenance treatment by 1)2 rituximab infusions mg at D1, D15 then every 6 months until
month 18 (i.e. a total of 5 infusions), at the dose of 500 mg. 2) 1 rituximab infusion at the
dose of 500 mg at D0 then ANCA status and CD19+ lymphocyte count will be monitored every 3
months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to
0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. After the 18
month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy,
patients will be followed for an additional 10 month period. Patients with granulomatosis
with polyangiitis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Number of relapses
Secondary Outcome
Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies)
Condition
Granulomatosis With Polyangiitis
Intervention
Rituximab (Arm B)
Study Arms / Comparison Groups
Rituximab infusion according biological parameters
Description: Rituximab infusion based on ANCA and CD19 lymphocytes
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
166
Start Date
November 16, 2012
Completion Date
April 5, 2016
Primary Completion Date
April 5, 2016
Eligibility Criteria
Inclusion Criteria:
- Granulomatosis with Polyangiitis Or microscopic polyangiitis complying Or
kidney-limited disease With or without detectable ANCA (anti-neutrophil cytoplasmic
antibodies) at the time of diagnosis or relapse, and at remission.
- Who have achieved remission using a treatment combining corticosteroids and an
immunosuppressive agent, including corticosteroids, cyclophosphamide IV or oral (the
use of another immunosuppressant is allowed, according to the current French
guidelines, as well as plasma exchanges and/or IV immunoglobulins, or rituximab).
- Interval of 1 month between the end of the immunosuppressant treatment and the
randomization time if cyclophosphamide or methotrexate were used, interval between 4
and 6 months if rituximab was used
- Age > 18 years without age limit higher when the diagnosis is confirmed.
- Informed and having signed the consent form to take part in the study.
Exclusion Criteria:
- Other systemic vasculitis
- Secondary vasculitis (following neoplastic disease or an infection in particular)
- Induction treatment with a regimen not corresponding to that recommended in France.
- Patient who has not achieved remission.
- Incapacity or refusal to understand or sign the informed consent form.
- Incapacity or refusal to adhere to treatment or perform the follow-up examinations
required by the study. Non-compliance
- Allergy, documented hypersensitivity or contraindication to the study medication
(cyclophosphamide, corticosteroids, azathioprine, rituximab)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibodies.
- Pregnancy, breastfeeding. Women of childbearing age must use a reliable method of
contraception throughout the duration of immunosuppressive treatment up to 1 year
after the last infusion of rituximab
- Infection by HIV, HCV or HBV
- Progressive, uncontrolled infection requiring a prolonged treatment (tuberculosis, HIV
infection, etc.).
- Severe infection declared during the 3 months before randomization (CMV, HBV, HHV8,
HCV, HIV, tuberculosis).
- Progressive cancer or malignant blood disease diagnosed during the 5 years before the
diagnosis of vasculitis. Patients suffering from non-metastatic prostate cancer or
those cured of a cancer or a malignant blood disorder for more than 5 years and not
taking any antineoplastic agents for more than 5 years may be included.
- Participation in another clinical research protocol during the 4 weeks before
inclusion.
- Any medical or psychiatric disorder which, in the investigator's opinion, may prevent
the administration of treatment and patient follow-up according to the protocol,
and/or which may expose the patient to a too greater risk of an adverse effect.
- No social security
- Churg and Strauss syndrome
- Viral, bacterial or fungic or mycobacterial infection uncontrolled in the 4 weeks
before the inclusion
- History of deep tissue infection (fasciitis, osteomyelitis, septic arthritis)in the
first year before the inclusion
- History of chronic and severe or recurrent infection or history of preexisting disease
predisposing to severe infection
- Severe immunodepression
- Administration of live vaccine in the four weeks before inclusion
- Severe chronic obstructive pulmonary diseases (VEMS < 50 % or dyspnea grade III)
- Chronic heart failure stade III and IV (NYHA)
- History of recent acute coronary syndrome, unrelated to vasculitis
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Loic Guillevin, MD, PhD, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT01731561
Organization ID
P110146
Secondary IDs
2012-001963-66
Responsible Party
Sponsor
Study Sponsor
Assistance Publique - Hôpitaux de Paris
Study Sponsor
Loic Guillevin, MD, PhD, Study Chair, Cochin Hospital, Paris, France
Verification Date
February 2018