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

• ClinicalTrials.gov Identifier: NCT01156922
• Recruitment Status: Terminated
• First Posted: July 5, 2010
• Last Update Posted: April 12, 2016
• Sponsor: Haukeland University Hospital
• Information provided by (Responsible Party): Haukeland University Hospital

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.

Condition or disease	Intervention/treatment	Phase
Chronic Fatigue Syndrome; Myalgic Encephalomyelitis	Drug: Rituximab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: June 2010
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 2016

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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 ]
   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)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 66 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Norway

Department of Oncology and Medical Physics, Haukeland University Hospital

Bergen, Norway, N-5021

Sponsors and Collaborators

Haukeland University Hospital

Investigators

• Principal Investigator: Olav Mella, PhD, MD; Haukeland University Hospital

More Information

Publications:

Fluge Ø, 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.

• Responsible Party: Haukeland University Hospital
• ClinicalTrials.gov Identifier: NCT01156922
• Other Study ID Numbers: 2010/1321
• First Posted: July 5, 2010
• Last Update Posted: April 12, 2016
• Last Verified: April 2016

Keywords provided by Haukeland University Hospital:

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

Additional relevant MeSH terms:

Fatigue Syndrome, Chronic; Encephalomyelitis; Myalgia; Syndrome; Fatigue; Disease; Pathologic Processes; Virus Diseases; Infections; Muscular Diseases; Musculoskeletal Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Central Nervous System Infections; Musculoskeletal Pain; Pain; Neurologic Manifestations; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents