Clinical trial NCT02444091: Cyclophosphamide in Myalgic Encephalopathy/ Chronic Fatigue Syndrome (ME/CFS)
Official title: Cyclophosphamide in Myalgic Encephalopathy/ Chronic Fatigue Syndrome (ME/CFS). Part A: an Open Label Phase-II Study With Six Intravenous Cyclophosphamide Infusions Four Weeks Apart, and Follow-up for 12 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Fatigue Syndrome (CFS)
Myalgic Encephalomyelitis (ME)
Keywords: Chronic Fatigue Syndrome
Myalgic Encephalomyelitis (ME)
Cyclophosphamide
Immunomodulatory treatment
CFS
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: The Kavli Foundation
name: Oslo University Hospital
First posted: 2015-05-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Significant clinical improvements of ME/CFS symptoms were observed in two patients with long-standing ME/CFS who received adjuvant chemotherapy including cyclophosphamide for breast cancer, also in one ME/CFS patient who received chemotherapy including iphosphamide for Hodgkin lymphoma.

Three pilot ME/CFS patients were thereafter treated with six intravenous infusions four weeks apart, in two of these with a significant clinical response.

The hypothesis is that a subset of ME/CFS patients have an activated immune system, and that ME/CFS symptoms may be alleviated by treatment with cyclophosphamide as intravenous pulse infusions four weeks apart, six infusions in total.

The purpose of the present study is to treat ME/CFS patients with cyclophosphamide as intravenous pulse infusions four weeks apart, six infusions in total. The effects on ME/CFS symptoms and tolerability/side effects during 12 months follow-up will be registered, and additional tests will be performed to objectively register changes in physical ability during follow-up. Studies to investigate possible large vessel endothelial dysfunction and skin microvascular dysfunction will be performed before start of intervention and during follow-up.


Eligibility criteria: Inclusion Criteria:

* Patients with ME/CFS according to "Canadian" criteria (2003)
* Duration of ME/CFS at least 2 years
* Mild/Moderate, Moderate, Moderate/Severe and Severe ME/CFS may be included
* Age 18-65 years
* Signed informed consent

Exclusion Criteria:

* Patients with fatigue who do not comply by the diagnostic "Canadian" criteria (2003) for ME/CFS
* Duration of ME/CFS less than 2 years
* Mild ME/CFS
* Very severe ME/CFS (bedridden requiring help for all tasks)
* Patients where the workup uncovers other pathology as possible cause of symptoms
* Pregnancy or breast feeding
* Previous malignant disease (except basal cell carcinoma of skin and cervical carcinoma in situ/dysplasia)
* Previous long-term systemic treatment with immunosuppressive agents (e.g. azathioprine, ciclosporin, mycophenolate mofetil). Except steroid treatment for e.g. obstructive lung disease or autoimmune diseases such as e.g. ulcerative colitis
* Serious endogenous depression
* Lack of ability to complete the study including follow-up
* Reduced renal function (creatinine \> 1.5 x UNL)
* Reduced liver function (bilirubin or transaminases \> 1.5 x UNL)
* Known hypersensitivity to cyclophosphamide or metabolites
* Reduced bone marrow function
* Ongoing cystitis or urinary tract obstruction
* Known HIV positivity, previous hepatitis B or hepatitis C, or reason to suspect other ongoing and clinically relevant infection

Primary outcomes:
measure: Fatigue score, selfreported
timeFrame: Within 12 months follow-up
measure: Overall response
timeFrame: Within 12 months follow-up
Secondary outcomes:
measure: Short Form-36 (SF-36)
timeFrame: Recorded at baseline, and at 3, 6, 9 and 12 months follow-up.
measure: Physical activity (Sensewear armband)
timeFrame: Recorded at baseline, at 7-9 months, and at 11-12 months
measure: Cardiopulmonary exercise tests for two following days
timeFrame: At baseline, and repeated at 7-9 months, and 11-12 months
measure: Self-recorded Function level
timeFrame: At baseline, and at 3, 6, 9 and 12 months follow-up
measure: Fatigue Severity Scale
timeFrame: Baseline, 3, 6, 9 and 12 months
measure: Longest continuous response duration
timeFrame: Within 12 months follow-up
measure: Sustained clinical response at 12 months
timeFrame: Assessment at end of follow-up (12 months)
measure: Safety and tolerability
timeFrame: Continuously within the study period of 12 months
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Dept. of Oncology, Haukeland University Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Mella Olav, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Haukeland University Hospital
name: Øystein Fluge, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Fluge O, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Naess H, Dahl O, Nyland H, Mella O. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. PLoS One. 2011;6(10):e26358. doi: 10.1371/journal.pone.0026358. Epub 2011 Oct 19.
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.
citation: Rekeland IG, Fossa A, Lande A, Ktoridou-Valen I, Sorland K, Holsen M, Tronstad KJ, Risa K, Alme K, Viken MK, Lie BA, Dahl O, Mella O, Fluge O. Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study. Front Med (Lausanne). 2020 Apr 29;7:162. doi: 10.3389/fmed.2020.00162. eCollection 2020.