Clinical trial NCT01156922: B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Very Severe Chronic Fatigue Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Fatigue Syndrome
Myalgic Encephalomyelitis
Keywords: Chronic fatigue syndrome
CFS
Myalgic encephalomyelitis
Rituximab
B-cell depletion
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
First posted: 2010-07-05
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 66
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes
timeFrame: Major response of at least six weeks duration, independent on when occuring, during the follow-up period
Secondary outcomes:
measure: Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes.
timeFrame: At 3, 6, 10, 15, 20, 24, 30, 36 months after intervention
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Department of Oncology and Medical Physics, Haukeland University Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Olav Mella, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fluge O, Mella O. Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series. BMC Neurol. 2009 Jul 1;9:28. doi: 10.1186/1471-2377-9-28.
citation: Fluge O, Risa K, Lunde S, Alme K, Rekeland IG, Sapkota D, Kristoffersen EK, Sorland K, Bruland O, Dahl O, Mella O. B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment. PLoS One. 2015 Jul 1;10(7):e0129898. doi: 10.1371/journal.pone.0129898. eCollection 2015.