Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis

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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