B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Very Severe Chronic Fatigue Syndrome
Primary Purpose
Chronic Fatigue Syndrome, Myalgic Encephalomyelitis
Status
Terminated
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Fatigue Syndrome focused on measuring Chronic fatigue syndrome, CFS, Myalgic encephalomyelitis, Rituximab, B-cell depletion
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
Sites / Locations
- Department of Oncology and Medical Physics, Haukeland University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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)
Full Information
NCT ID
NCT01156922
First Posted
July 2, 2010
Last Updated
April 11, 2016
Sponsor
Haukeland University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01156922
Brief Title
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
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Terminated
Why Stopped
Difficulties in logistics handling the very severe patients (travel, hospital stay, follow-up)
Study Start Date
June 2010 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Haukeland University Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Fatigue Syndrome, Myalgic Encephalomyelitis
Keywords
Chronic fatigue syndrome, CFS, Myalgic encephalomyelitis, Rituximab, B-cell depletion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes
Description
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.
Time Frame
Major response of at least six weeks duration, independent on when occuring, during the follow-up period
Secondary Outcome Measure Information:
Title
Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes.
Description
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)
Time Frame
At 3, 6, 10, 15, 20, 24, 30, 36 months after intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
66 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olav Mella, PhD, MD
Organizational Affiliation
Haukeland University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Oncology and Medical Physics, Haukeland University Hospital
City
Bergen
ZIP/Postal Code
N-5021
Country
Norway
12. IPD Sharing Statement
Citations:
PubMed Identifier
19566965
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.
Results Reference
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B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Very Severe Chronic Fatigue Syndrome
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