ANCA associated vasculitis
Conditions
Interventions
Trade Name: Cyclophosphamide
Product Name: Cyclophosphamide
Product Code: 5009111000001105
Pharmaceutical Form: Powder for infusion
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 4.1. Inclusion criteria Subjects enrolled in the study must meet the following inclusion criteria: 1) Clinical diagnosis of granulomatosis with polyangiitis (GPA) or microscopic Polyangiitis (MPA), consistent with Chapel-Hill Consensus Conference definitions26 2) Aged at least 18 years, with newly-diagnosed or relapsed AAV with ‘generalised disease’, defined as involvement of at least one major organ (e.g. kidney, lung, heart, peripheral or central nervous system), requiring induction treatment with cyclophosphamide or rituximab 3) Positive test for anti-PR3 or anti-MPO (current or historic) 4) Willing and able to give written Informed Consent and to comply with the requirements of the study protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 4.2. Exclusion criteria Subjects will be excluded from participation if they meet any of the following exclusion criteria: 1) Pregnant or breast-feeding 2) Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum beta-HCG 3) Significant hypogammaglobulinemia (IgG 3 times the upper limit of normal before start of dosing 10) Have a CD19 count of 3000mg methylprednisolone equivalent, within 4 weeks prior to screening 14) Immunization with a live vaccine 1 month before screening 15) History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the patient at unacceptable risk for study participation. 16) Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In this randomized study the primary objective is to prove the superiority of combination treatment RTX with cyclophosphamide to achieve a state of MRA in AAV patients as compared to RTX alone. The primary objective is to assess the time to an ANCA negative test. ;Secondary Objective: Secondary objectives are: - time to ANCA return - duration of B-cell depletion - composition of the memory B-cell and plasma cell compartment before and after treatment - to investigate whether MRA is associated with disease flares - to investigate whether MRA is associated with (a shorter) time to a disease flares - to investigate whether the presence or absence of MRA after RTX can guide a personalized treatment - to assess the safety parameters of each treatment arm including adverse events according to WHO toxicity criteria, time to immune reconstitution and recording of infectious events;Primary end point(s): The primary immunological parameter will be the time to seroconversion of ANCA to negative, i.e. below the detection range of a high-quality ANCA immunoassay.;Timepoint(s) of evaluation of this end point: SCR BL 2 4 8 12 16 20 24 32 40 48 56 64 72 80 88 96 104 EoS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - assess the time to ANCA return defined as seroconversion to positive on at least 2 consecutive visits (the time of the first is then representative time of seroconversion) OR a doubling of the ANCA serum levels PR3 or MPO ELISA test compared to a previously achieved nadir - duration of B-cell depletion defined as time taken to detect a repopulation of B-cells above the detection limit of standard flowcytometry (i.e. > 1x106 cells/L) - composition of the memory B-cell and plasma cell compartment before and after treatment using standard and high-sensitivity flowcytometry - to investigate whether MRA is associated with disease flares where degrees of MRA are defined as seroconversion of ANCA to negative with or without B-cell depletion - to investigate whether MRA is associated with (a shorter) time to a disease flares - to assess the safety parameters of each treatment arm including adverse events according to WHO toxicity criteria and recording of infectious events;Timepoint(s) of evaluation of this end point: SCR BL 2 4 8 12 16 20 24 32 40 48 56 64 72 80 88 96 104 EoS experimental high sensitivity flow cytometry: scr, bl, 4, 12, 24, 40, 56, 72, 88, 104, eos | — |
Countries
Netherlands
Contacts
Public ContactTeng
Leiden university medical centre
Outcome results
None listed