Clinical trial NCT04640818: Safety and Efficacy of Cladribine Therapy After Anti CD20 Therapy
Official title: Safety and Efficacy of a Therapy With Cladribine Following a Treatment With Anti CD20 Compounds in Relapsing Multiple Sclerosis Patients: a Pilot Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Sclerosis
Keywords: anti CD20 therapy
cladribine
Lead sponsor: Ospedale Civico, Lugano
Sponsor class: OTHER_GOV
Collaborators: name: Merck AG Switzerland
First posted: 2020-11-23
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with relapsing multiple sclerosis

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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Non relapsing MS;
* Pregnancy - breastfeeding;
* Contraindications to perform MRI;
* Contraindication to receive cladribine or to continue anti CD therapies

Primary outcomes:
measure: Changes in IgG serum concentrations in Cald-Group
timeFrame: 6 months
measure: Changes in IgM serum concentrations in Cald-Group
timeFrame: 6 months
measure: Changes in IgG serum concentrations in Clad-Group
timeFrame: 12 months
measure: Changes in IgM serum concentrations in Clad-Group
timeFrame: 12 months
Secondary outcomes:
measure: Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
timeFrame: 6 months
measure: Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
timeFrame: 6 months
measure: Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
timeFrame: 12 months
measure: Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
timeFrame: 12 months
measure: Proportion of patients reaching NEDA -3
timeFrame: 12 months
measure: Annualized relapse rate (ARR) over 12 months after switching to cladribine as compared to patients continuing anti CD20 therapies
timeFrame: 12 months
measure: Proportion of patients with disability progression
timeFrame: 6 months
measure: Proportion of patients with disability progression
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: Changes in serum neurofilament light chain concentration
timeFrame: 12 months
Other outcomes:
measure: Frequency of infections
timeFrame: 6 months
measure: Frequency of infections
timeFrame: 12 months
measure: Intensity of infections
timeFrame: 6 months
measure: Intensity of infections
timeFrame: 12 months
measure: Proportion of patients with abnormal creatinine values of clinical relevance
timeFrame: 6 months
measure: Proportion of patients with abnormal creatinine values of clinical relevance
timeFrame: 12 months
measure: Proportion of patients with abnormal ASAT values of clinical relevance
timeFrame: 6 months
measure: Proportion of patients with abnormal ASAT values of clinical relevance
timeFrame: 12 months
measure: Proportion of patients with abnormal ALAT values of clinical relevance
timeFrame: 6 months
measure: Proportion of patients with abnormal ALAT values of clinical relevance
timeFrame: 12 months
measure: Proportion of patients with any abnormal hematology values of clinical relevance
timeFrame: 6 months
measure: Proportion of patients with any abnormal hematology values of clinical relevance
timeFrame: 12 months
Locations:
city: Lugano
country: Switzerland
facility: Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano
state: Ticino
Study officials:
affiliation: Ospedale Regionale di Lugano, Neurocentro della Svizzera italiana, Centro Sclerosi multipla
name: Claudio Gobbi, MD
role: PRINCIPAL_INVESTIGATOR
References: