B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Very Severe Chronic Fatigue Syndrome

Study Overview
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Brief Summary
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Based on pilot patient observations, and experience from the prior study KTS-1-2008, the investigators anticipate that severely affected chronic fatigue syndrome patients may benefit from B-cell depletion therapy using Rituximab induction with maintenance treatment. The hypothesis is that at least a subset of chronic fatigue syndrome (CFS) patients have an activated immune system involving B-lymphocytes, and that prolonged B-cell depletion may alleviate symptoms. An approved amendment (April 15th 2011): the study will be extended with up to 5 patients. For up to 5 patients in the study, standard plasma exchange may be performed 2-3 weeks prior to start of B-lymphocyte depletion using Rituximab (as in the protocol). Approved amendment (December 2011): for patients with gradual improvement in CFS/ME symptoms after 12 months follow-up, but not having reached a clear response, up to 6 additional Rituximab infusions (500 mg/m2, max 1000 mg) may be given during the following 12 months period.

Official Title
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B-lymphocyte Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Severely Affected Chronic Fatigue Syndrome Patients. An Open Label Phase II Study With Rituximab Induction and Maintenance Treatment for Patients in WHO Performance Status III-IV

Conditions
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Chronic Fatigue Syndrome, Myalgic Encephalomyelitis

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients severely affected by chronic fatigue syndrome, in WHO performance status III or IV. age 18-66 years informed consent Exclusion Criteria: patients with fatigue, not fulfilling criteria for CFS pregnancy or lactation previous malignant disease except basal cell carcinoma of skin and cervical carcinoma in situ previous major immunological disease, except autoimmune diseases such as diabetes mellitus or thyroiditis endogenous depression lack of ability to comply by the protocol multi-allergy with risk of serious drug reaction reduced renal function (creatinin > 1.5 x upper normal limit [UNL]) reduced liver function (bilirubin or transaminases > 1.5 x UNL) HIV positivity evidence of clinically significant infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 66 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>Rituximab induction two infusions (500 mg/m2, max 1000 mg) two weeks apart, followed by maintenance Rituximab infusions (500 mg/m2, max 1000 mg) after 3, 6, 10 and 15 months. | Drug: Rituximab<br>* Two infusions of Rituximab 500 mg/m2 (max 1000 mg) given two weeks apart, followed by maintenance Rituximab infusions 500 mg/m2 (max 1000 mg) at 3, 6, 10, and 15 months. For up to 5 patients in the study, standard plasma exchange (one plasma volume, up to 5 treatments, during 1-2 weeks) will be performed 2-3 weeks prior to start of Rituximab therapy. Amendment: for patients with gradual improvement in CFS/ME symptoms after 12 months follow-up, but not having reached a clear response, up to 6 additional Rituximab infusions (500 mg/m2, max 1000 mg) may be given during the following 12 months period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes | The primary endpoint is defined as major response of the CFS symptoms, of at least six weeks duration, independent on when during 36 months follow-up the response period(s) occurs. Single such response periods, and the sum of these, are recorded. | Major response of at least six weeks duration, independent on when occuring, during the follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes. | The secondary outcome measures are effect on the CFS symptoms, by evaluation at 3, 6, 10, 15, 20, 24, 30, and 36 months after first intervention (i.e. first Rituximab infusion) | At 3, 6, 10, 15, 20, 24, 30, 36 months after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic fatigue syndrome, CFS, Myalgic encephalomyelitis, Rituximab, B-cell depletion