Safety and Efficacy of Cladribine Therapy After Anti CD20 Therapy

Safety and Efficacy of a Therapy With Cladribine Following a Treatment With Anti CD20 Compounds in Relapsing Multiple Sclerosis Patients: a Pilot Study

Sponsors

Lead Sponsor: Claudio Gobbi

Collaborator: Merck AG Switzerland

Source Ospedale Civico, Lugano
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).

Overall Status Recruiting
Start Date 2020-12-17
Completion Date 2022-10-31
Primary Completion Date 2022-10-31
Study Type Observational
Primary Outcome
Measure Time Frame
Changes in IgG serum concentrations in Cald-Group 6 months
Changes in IgM serum concentrations in Cald-Group 6 months
Changes in IgG serum concentrations in Clad-Group 12 months
Changes in IgM serum concentrations in Clad-Group 12 months
Secondary Outcome
Measure Time Frame
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies 6 months
Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies 6 months
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies 12 months
Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies 12 months
Proportion of patients reaching NEDA -3 12 months
Annualized relapse rate (ARR) over 12 months after switching to cladribine as compared to patients continuing anti CD20 therapies 12 months
Proportion of patients with disability progression 6 months
Proportion of patients with disability progression 12 months
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
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
Changes in serum neurofilament light chain concentration 12 months
Enrollment 45
Condition
Intervention

Intervention Type: Drug

Intervention Name: Cladribine Oral Tablet

Description: Treatment according to the label and medical prescription

Arm Group Label: CLAD-GROUP

Other Name: Mavenclade

Intervention Type: Drug

Intervention Name: Rituximab

Description: Treatment according to the label and medical prescription

Arm Group Label: CD20-GROUP

Other Name: Mabthera, Rixathon

Intervention Type: Drug

Intervention Name: Ocrelizumab

Description: Treatment according to the label and medical prescription

Arm Group Label: CD20-GROUP

Other Name: Ocrevus

Eligibility

Sampling Method:

Non-Probability Sample

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

80 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Claudio Gobbi, MD Principal Investigator Ospedale Regionale di Lugano, Neurocentro della Svizzera italiana, Centro Sclerosi multipla
Overall Contact

Last Name: Claudio Gobbi, MD

Phone: +41 91 811 6921

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano Claudio Gobbi, Dr med. +41 811 91 6479 [email protected]
Location Countries

Switzerland

Verification Date

2021-01-01

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Ospedale Civico, Lugano

Investigator Full Name: Claudio Gobbi

Investigator Title: Head Physician

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Label: CLAD-GROUP

Description: Patients with cladribine therapy

Label: CD20-GROUP

Description: Patients with anti CD20 therapy (ocrelizumab or rituximab)

Patient Data No
Study Design Info

Observational Model: Cohort

Time Perspective: Prospective

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