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

NCT01156922 | Terminated Phase 2

• 1 other identifier: 2010/1321
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Fatigue Syndrome; Myalgic Encephalomyelitis

Keywords

Chronic fatigue syndrome; CFS; Myalgic encephalomyelitis; Rituximab; B-cell depletion

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Symptom alleviation, as compared to baseline, measured by standardized self-reports and quality of life schemes.

  At 3, 6, 10, 15, 20, 24, 30, 36 months after intervention

Study Arms (1)

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.

Drug: Rituximab

Interventions

Rituximab DRUG

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.

Rituximab

Eligibility Criteria

• Age: 18 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients severely affected by chronic fatigue syndrome, in WHO performance status III or IV.
• age 18-66 years
• informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (1)

Department of Oncology and Medical Physics, Haukeland University Hospital

Bergen, N-5021, Norway

Location

Related Publications (2)

• 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.

  PMID: 19566965 BACKGROUND

• 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.

  PMID: 26132314 RESULT

MeSH Terms

Conditions

Fatigue Syndrome, Chronic

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Olav Mella, PhD, MD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 5, 2010
• Study Start: June 1, 2010
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: March 4, 2024

Record last verified: 2024-03

Locations

NO (1)