Safety and Efficacy of Cladribine Therapy After Anti CD20 Therapy
- Conditions
- Multiple Sclerosis
- Interventions
- Registration Number
- NCT04640818
- Lead Sponsor
- Claudio Gobbi
- Brief Summary
Prolonged anti CD20 therapy for the treatment of active multiple sclerosis leading to continuous B cell depletion is associated with hypogammaglobulinemia predisposing to a potentially increased risk of serious infections, particularly in the more disabled and aged patients. No data have been published on the sequential use of anti CD20 therapies and cladribine, that is thought to act as an immune reconstitution agent. his study aims at investigating IgG and IgM serum concentration changes at 6 and 12 months after switching to cladribine in patients previously treated with anti CD20 therapies (ie, ocrelizumab ≥1.8 gr or rituximab 3.0 gr) for ≥18 months, as compared to continued anti CD20 therapies.
- Detailed Description
The study population will include patients with remitting relapsing multiple sclerosis consulting the Multiple Sclerosis Center of Neurocenter of Southern Switzerland.
Enrolled patients will have 5 Study Visits, one every 3 months according to clinical practice. At visits at 3 and 6 months only adverse events will be collected for study purposes. Clinical assessments will be performed at baseline, Month 6 and Month 12. Clinical assessments correspond to medical exams performed routinely in MS patients treated with anti CD20 or cladribine therapy: clinical assessments, monitoring haemoglobin parameters, serum immunoglobulins, liver and renal function.(6, 12 months), radiological disability progression and biomarker of ongoing neurodegeneration (12 months).
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 45
- Relapsing MS according to Lublin;
- Treatment with ocrelizumab or rituximab for ≥18 months and having received 1.8 / 3.0 gr, respectively;
- CLAD_GROUP: Planning to switch to cladribine because of concerns about increased risks of infections related to hypogammaglobulinemia developing during long term anti CD20 therapies or a documented decrease of ≥10% IgG and/or IgM compared to pre- anti CD20 therapy;
- or CD20_GROUP: no need to stop CD20 therapy due decrease of ≥10% IgG and/or IgM, or increased risk of infections related to hypogammaglobulinemia or other reasons, continued anti CD20 therapies clinically indicated;
- EDSS ≤7.0;
- Age >18 years.
- Non relapsing MS;
- Pregnancy - breastfeeding;
- Contraindications to perform MRI;
- Contraindication to receive cladribine or to continue anti CD therapies
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description CLAD-GROUP Cladribine Oral Tablet Patients with cladribine therapy CD20-GROUP Rituximab Patients with anti CD20 therapy (ocrelizumab or rituximab) CD20-GROUP Ocrelizumab Patients with anti CD20 therapy (ocrelizumab or rituximab)
- Primary Outcome Measures
Name Time Method Changes in IgG serum concentrations in Cald-Group 6 months Standard laboratory test
Changes in IgM serum concentrations in Cald-Group 6 months Standard laboratory test
Changes in IgM serum concentrations in Clad-Group 12 months Standard laboratory test
Changes in IgG serum concentrations in Clad-Group 12 months Standard laboratory test
- Secondary Outcome Measures
Name Time Method Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies 12 months Standard laboratory test
Number/volume of cumulative new T2/ enlarging lesions at brain and spinal MRI over 12 months after switching to cladribine, as compared to patients continuing anti CD20 therapies 12 months Evaluation of MRI
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies 12 months Standard laboratory test
Number/volume of cumulative Gd enhancing lesions at brain and spinal MRI over 12 months after switching to cladribine, as compared to patients continuing anti CD20 therapies 12 months Evaluation of MRI
Changes in serum neurofilament light chain concentration 12 months single-molecule array (Simoa) assay
Annualized relapse rate (ARR) over 12 months after switching to cladribine as compared to patients continuing anti CD20 therapies 12 months ARR will be calculated based on recorded number of relapses
Proportion of patients with disability progression 12 months Expanded disability scale 0-6 (6 worst outcome)
Proportion of patients reaching NEDA -3 12 months NEDA -3: no relapses, no disability progression, no new/enlarging or Gd enhancing brain or spinal MR lesions
Trial Locations
- Locations (1)
Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano
🇨🇭Lugano, Ticino, Switzerland