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

NCT ID: NCT01156922

Last Updated: 2024-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2016-04-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: 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.

Interventions

Rituximab

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 66 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Haukeland University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olav Mella, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Haukeland University Hospital

Locations

Department of Oncology and Medical Physics, Haukeland University Hospital

Bergen, , Norway

Countries

Norway

References

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.

Reference Type: BACKGROUND

PMID: 19566965 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26132314 (View on PubMed)

Other Identifiers

2010/1321

Identifier Type: -

Identifier Source: org_study_id