Chronic Fatigue SyndromePhase 2NCT01156922
B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Very Severe Chronic Fatigue Syndrome
A Phase 2 study testing Rituximab in people with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis, run by Haukeland University Hospital at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 66 years
- Conditions the study is for
- Chronic Fatigue Syndrome, Myalgic Encephalomyelitis
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteNorway
- Study dates
- Jun 2010to Apr 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 66 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients severely affected by chronic fatigue syndrome, in WHO performance status III or IV.
- age 18-66 years
- informed consent
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Norway1 site
Department of Oncology and Medical Physics, Haukeland University Hospital
Bergen, N-5021
About this study
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
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.
Read more
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.
- Being tested
- Rituximab
- Keywords
- Chronic fatigue syndrome, CFS, Myalgic encephalomyelitis, Rituximab, B-cell depletion
- Medical subject headings
- Fatigue Syndrome, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | 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. Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Major response of at least six weeks duration, independent on when occuring, during the follow-up period
Secondary outcomes (1)
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)
Measured: At 3, 6, 10, 15, 20, 24, 30, 36 months after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2010 (estimated)
- Study startJun 2010
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: Difficulties in logistics handling the very severe patients (travel, hospital stay, follow-up)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Fatigue SyndromeStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olav Mella, PhD, MD, Principal investigator, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01156922
- Sponsor's protocol ID
- 2010/1321
- Status last verified
- Mar 2024
- First submitted
- 2 Jul 2010
- Last updated
- 4 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19566965Fluge 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.
PubMed 26132314
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01156922
- Acronym / sponsor ID
- 2010/1321
- Keywords
- Chronic fatigue syndrome, CFS, Myalgic encephalomyelitis, Rituximab, B-cell depletion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties in logistics handling the very severe patients (travel, hospital stay, follow-up)
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 5 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabRituximab 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. |
Who may qualify
- Ages
- 18 to 66 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- patients severely affected by chronic fatigue syndrome, in WHO performance status III or IV.
- age 18-66 years
- informed consent
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabTwo 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. | Drug | Rituximab |
Primary outcome
Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes
Time frame: Major response of at least six weeks duration, independent on when occuring, during the follow-up period
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.
1 secondary outcome
Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes.
Time frame: At 3, 6, 10, 15, 20, 24, 30, 36 months after intervention
Results and safety
The study was stopped early (reason given: Difficulties in logistics handling the very severe patients (travel, hospital stay, follow-up)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2024.
- Background: PubMed 19566965Fluge 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 publication: PubMed 26132314Fluge 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olav Mella, PhD, MD principal investigator
Haukeland University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis, run by Haukeland University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulties in logistics handling the very severe patients (travel, hospital stay, follow-up)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes (time frame: Major response of at least six weeks duration, independent on when occuring, during the follow-up period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01156922, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2024.