A Phase 3 interventional study of Rituximab and endoxan in ANCA Associated Vasculitis, sponsored by Leiden University Medical Center. Status unknown at 4 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-12-14.
Sponsored by Leiden University Medical Center · Phase 3, Interventional, and Treatment
Most recent insights in the treatment for patients with ANCA-associated vasculitis (AAV) have demonstrated that 'tailored' maintenance treatment with rituximab (RTX) is effective to achieve durable remission of disease. As such, RTX re-treatment can be tailored on the basis of relevant clinical and immunological parameters in AAV patients. Now, the present study intends to evaluate whether combining rituximab with cyclophosphamide is superior to current standard of care with rituximab only to induce a favorable clinical and immunological state in AAV patients and can thereby reduce the number of tailored re-treatments with rituximab.
Objectives: The primary objective is to prove that the combination of RTX and low-dose CYC reduces the number of RTX infusions needed to maintain clinical remission over 2 years. The secondary objectives are measurements for minimal residual auto-immunity (MRA) such as time to ANCA seronegativity, proportion of seronegativity, time to ANCA return, proportion of ANCA return, duration of B-cell depletion and the composition of the memory B-cell and plasma cell populations. Other secondary objectives are the potential association between MRA and disease flares, and the evaluation of (severe) adverse events, cost-effectiveness and quality of life Study design: open-label, multicenter, 1:1 randomized, prospective study Study population: Adult AAV patients with a clinical diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have 'generalised disease' and a positive ANCA-test for anti-PR3 or anti-MPO.
Intervention: In addition to standard of care corticosteroid therapy, AAV patients will be randomized to receive either standard induction therapy with 2 infusions of RTX 1000 mg or induction therapy combining 2 infusions of RTX 1000 mg with 6 infusions of low dose intravenous cyclophosphamide 500mg. Thereafter, as part of standard of care patients will receive tailored RTX re-treatment as maintenance therapy.
Main study parameters: AAV patients will be evaluated for the cumulative number of events for tailored RTX retreatments needed to maintain clinical remission over 2 years. Also, AAV patients will be evaluated for MRA by prospectively and consecutively studying ANCA levels and B-cell depletion by standard flowcytometry at predefined timepoints. Additionally, the study will perform safety and toxicity monitoring according to WHO toxicity criteria and evaluate the clinical response, the number of moderate and severe flares during study follow-up, the cost-effectiveness, and the quality of life of patients.
Study duration: 2 years
142 studies on the registry are indexed under Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; 72 are open to participants now.
This study's planned enrollment of 100 is above the median of 32 across 105 interventional studies indexed under Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.
Browse Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis studies →Leiden University Medical Center is the lead sponsor of 333 studies on the registry; 109 are open to participants now.
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Subjects enrolled in the study must meet the following inclusion criteria:
Exclusion criteria:
Subjects will be excluded from participation if they meet any of the following exclusion criteria:
Active infection not compatible with start of remission-induction therapy in the opinion of the treating physician and/or investigator, e.g.:
Patients will be intravenously treated with Rituximab 1000mg (or biosimilar) in the first week and receive a 2nd dosage of 1000mg 14 days later. Before every infusion of Rituximab patients will receive intravenous methylprednisolone 100mg together with oral acetaminophen 1000 mg and and intravenous Tavegil 2 mg.
Drug: Rituximab · Drug: Methylprednisolone · Drug: Prednisolone
5.1.2. Cyclophosphamide Patients will be intravenously treated with a total of 6 infusions of cyclophosphamide 500mg every 2 weeks. Before every infusion of cyclophosphamide patients will receive intravenous granisetron to prevent nausea.
Drug: Rituximab · Drug: endoxan · Drug: Methylprednisolone · Drug: Prednisolone
Patients will be intravenously treated with Rituximab 1000mg (or biosimilar) in the first week and receive a 2nd dosage of 1000mg 14 days later. Before every infusion of Rituximab patients will receive intravenous methylprednisolone 100mg together with oral acetaminophen 1000 mg and and intravenous Tavegil 2 mg. At any time during the study, a rituximab biosimilar is allowed as a substitute for the bio-originator rituximab.
Also known as: anti-cd20
Patients will be intravenously treated with a total of 6 infusions of cyclophosphamide 500mg every 2 weeks. Before every infusion of cyclophosphamide patients will receive intravenous granisetron to prevent nausea.
Also known as: cyclophosphamide
Patients are given 1-3 pulses of 500mg methylprednisolone i.v. up to a maximum cumulative dose of 3000mg, taking into account any doses of intravenous methylprednisolone administered within 12 weeks prior to screening.
Also known as: solumedrol
after intravenous pulse methylprednisolone, oral prednisolone will be given at a dose of 1mg/kg daily and tapered according to the recommendations
Also known as: corticosteroid
Number of tailored RTX infusions
The primary outcome is the number of RTX infusions needed to maintain clinical remission over 2 years
Time frame: 2 years
Time
\- time to a ANCA negative test
Time frame: 2 years
ANCA reappearance
\- Percentage of patients that have ANCA return during follow-up
Time frame: 2 years
B cell depletion
\- duration of B-cell depletion
Time frame: 2 years
Remission and relaps rate
\- to compare disease controle between arms
Time frame: 2 years
Number of adverse events
\- 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
Time frame: 2 years
Quality of Life by AAV-PRO
assess quality of life by AAV-PRO
Time frame: 2 years
BVAS
Disease activity will be assessed by BVAS
Time frame: 2 years
concomitant immunosuppressants
Disease activity assessed by (the reduction of) concomitant immunosuppressants
Time frame: 2 years
Kidney function
Return of kidney function will be assessed.
Time frame: 2 years
Biomarker for inflammation
Disease activity assessed by ESR
Time frame: 2 years
Plan to share: No
This study is status unknown, as verified in Dec 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Cyclophosphamide
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis →
Leiden University Medical Center →