Safety and Efficacy of Cladribine Therapy After Anti CD20 Therapy

March 22, 2022 updated by: Claudio Gobbi

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

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.

Study Overview

Status

Active, not recruiting

Conditions

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).

Study Type

Observational

Enrollment (Anticipated)

45

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ticino
      • Lugano, Ticino, Switzerland, 6903
        • Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with relapsing multiple sclerosis

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
CLAD-GROUP
Patients with cladribine therapy
Treatment according to the label and medical prescription
Other Names:
  • Mavenclade
CD20-GROUP
Patients with anti CD20 therapy (ocrelizumab or rituximab)
Treatment according to the label and medical prescription
Other Names:
  • Mabthera, Rixathon
Treatment according to the label and medical prescription
Other Names:
  • Ocrevus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in IgG serum concentrations in Cald-Group
Time Frame: 6 months
Standard laboratory test
6 months
Changes in IgM serum concentrations in Cald-Group
Time Frame: 6 months
Standard laboratory test
6 months
Changes in IgG serum concentrations in Clad-Group
Time Frame: 12 months
Standard laboratory test
12 months
Changes in IgM serum concentrations in Clad-Group
Time Frame: 12 months
Standard laboratory test
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Time Frame: 6 months
Standard laboratory test
6 months
Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Time Frame: 6 months
Standard laboratory test
6 months
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Time Frame: 12 months
Standard laboratory test
12 months
Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Time Frame: 12 months
Standard laboratory test
12 months
Proportion of patients reaching NEDA -3
Time Frame: 12 months
NEDA -3: no relapses, no disability progression, no new/enlarging or Gd enhancing brain or spinal MR lesions
12 months
Annualized relapse rate (ARR) over 12 months after switching to cladribine as compared to patients continuing anti CD20 therapies
Time Frame: 12 months
ARR will be calculated based on recorded number of relapses
12 months
Proportion of patients with disability progression
Time Frame: 6 months
Expanded disability scale 0-6 (6 worst outcome)
6 months
Proportion of patients with disability progression
Time Frame: 12 months
Expanded disability scale 0-6 (6 worst outcome)
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
Time Frame: 12 months
Evaluation of MRI
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
Time Frame: 12 months
Evaluation of MRI
12 months
Changes in serum neurofilament light chain concentration
Time Frame: 12 months
single-molecule array (Simoa) assay
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of infections
Time Frame: 6 months
Safety endpoint
6 months
Frequency of infections
Time Frame: 12 months
Safety endpoint
12 months
Intensity of infections
Time Frame: 6 months

Safety endpoint, intensity will be rated according to the following definitions:

Mild: Awareness of a sign or symptom that does not interfere with the study participant's usual activity or is transient, resolved without treatment and with no sequelae; Moderate: Interferes with the study participant's usual activity and/or requires symptomatic treatment; Severe: Symptom(s) causing severe discomfort and significant impact of the study participant's usual activity and requires treatment.

Serious: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, or is otherwise considered as medically important.

6 months
Intensity of infections
Time Frame: 12 months

Safety endpoint, intensity will be rated according to the following definitions:

Mild: Awareness of a sign or symptom that does not interfere with the study participant's usual activity or is transient, resolved without treatment and with no sequelae; Moderate: Interferes with the study participant's usual activity and/or requires symptomatic treatment; Severe: Symptom(s) causing severe discomfort and significant impact of the study participant's usual activity and requires treatment.

Serious: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, or is otherwise considered as medically important.

12 months
Proportion of patients with abnormal creatinine values of clinical relevance
Time Frame: 6 months
Safety endpoint
6 months
Proportion of patients with abnormal creatinine values of clinical relevance
Time Frame: 12 months
Safety endpoint
12 months
Proportion of patients with abnormal ASAT values of clinical relevance
Time Frame: 6 months
Safety endpoint
6 months
Proportion of patients with abnormal ASAT values of clinical relevance
Time Frame: 12 months
Safety endpoint
12 months
Proportion of patients with abnormal ALAT values of clinical relevance
Time Frame: 6 months
Safety endpoint
6 months
Proportion of patients with abnormal ALAT values of clinical relevance
Time Frame: 12 months
Safety endpoint
12 months
Proportion of patients with any abnormal hematology values of clinical relevance
Time Frame: 6 months
Safety endpoint
6 months
Proportion of patients with any abnormal hematology values of clinical relevance
Time Frame: 12 months
Safety endpoint
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Principal Investigator: Claudio Gobbi, MD, Ospedale Regionale di Lugano, Neurocentro della Svizzera italiana, Centro Sclerosi multipla

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 17, 2020

Primary Completion (Anticipated)

October 31, 2022

Study Completion (Anticipated)

October 31, 2022

Study Registration Dates

First Submitted

November 18, 2020

First Submitted That Met QC Criteria

November 18, 2020

First Posted (Actual)

November 23, 2020

Study Record Updates

Last Update Posted (Actual)

March 23, 2022

Last Update Submitted That Met QC Criteria

March 22, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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