CycloME

CycloME is a clinical trial sponsored by the ME/CFS research group at the Department of Oncology and Medical Physics at Haukeland University Hospital, Bergen, Norway. Senior Consultant Øystein Fluge and Professor Olav Mella are the study supervisors. Kari Sørland, a nurse, is the national project coordinator. The Kavli Trust, a humanitarian foundation, is contributed to the trial by funding 50% of a nursing post for 12 months.

Cyclophosphamide
Cyclophosphamide, a chemotherapy and immunosuppressant drug, has been investigated as a treatment in ME/CFS. As with the rituximab studies, the potential efficacy with ME was stumbled on by accident after treating two breast cancer patients, who also had ME, with cyclophosphamide, and having the women report that their ME symptoms improved. Before treatment, a bedbound ME patient walked an average of 326 steps per day. After six infusions with cyclophosphamide, she was able to walk 13,000 steps daily.

CycloME part A​
The first cyclophosphamide trial was a single centre, unblinded study with 40 patients with mild/moderate to severe ME but not very severe ME. Some of the participants were previously treated with Rituximab. The Department of Oncology at Haukeland University Hospital was responsible for assessing which patients to include the trial, as well as administering the treatments. The Norwegian Radium Hospital, Oslo, took part in the trial as a treatment centre, administering treatments to a small group of patients from the Oslo area. The Canadian Consensus Criteria was used in selecting participants. All participants received six intravenous treatments of cyclophosphamide, each treatment four weeks apart. The participants was followed-up for one year. Each was given complete physical examinations and testing before and after treatment, and submitted regular reports on any changes in symptoms and physical function. The physical function testing included a measurement of activity via a Sensewear armband (a wearable device that measures physical activity and total energy expenditure expressed as Kcal), two-day Cardiopulmonary exercise tests for those who are able, and self-reporting fatigue scores. Adverse effects were tested for with physical examinations and laboratory tests. Side effects were expected to be minimal, because similar dosages have already been used in breast cancer and lymphoma trials, although some serious adverse responses did occur. Study results were published in 2020. Data analysis included comparing the group who received rituximab prior to those who did not.

CycloME part B
The Haukeland University Hospital ME/CFS research group found positive interim results from CycloME part A in over 40% of the patients, so began part B, although the trial was not extended to include patients with very severe ME. In part B, both treatment and follow-up were completed in collaboration with the patient’s local primary health service.

Study outcome measures
Primary Outcome Measures: Secondary Outcome Measures:
 * Self reported fatigue score, and
 * overall response as the effect of treatment on ME/CFS symptoms, both measured within a 12 months follow-up period.
 * Short-Form 36 (SF-36), recorded at baseline, and at 3, 6, 9 and 12 months follow-up,
 * Physical activity via a Sensewear armband, recorded at baseline, at 7-9 months, and at 11-12 months,
 * Cardiopulmonary exercise tests for two following days, performed at baseline, and repeated at 7-9 months, and 11-12 months,
 * Self-recorded Function level, recorded at baseline, and at 3, 6, 9 and 12 months follow-up,
 * Fatigue Severity Scale (FSS), completed at baseline, 3, 6, 9 and 12 months,
 * Longest duration of continuous response duration, measured by a self-reported fatigue score ≥ 4,5 (for at least 6 consecutive weeks) within 12 months follow-up,
 * Sustained clinical response at 12 months, defined as a fatigue score of at least 4.5 at 12 months follow-up, and
 * Safety and tolerability, including adverse events, measured by patient history, physical exam, and lab tests, performed every four weeks the first six months, thereafter at 6, 9 and 12 months follow-up. Adverse events were likely to include hair loss, vomiting, diarrhea, jaundice, leukopenia, anemia, thrombocytopenia, infections, allergic reactions and hemorrhagic cystitis, disturbed ovarian function. Information collection on possible toxicity continued after the formal 12 months study period.

The final follow up continued 3-4 years.

Side effects
Most patients reported one of two side effects, the most common being nausea, infections and constipation.

Results
Rekeland et al. (2020) found that responders roughly doubled the number of steps they could take, and were more likely to have mild/moderate or moderate ME/CFS. Over half of patients responded, with HLA-B allelles being linked to a much higher chance of response. Further trials of cyclophosphamide are planned.

Notable studies

 * 2020, Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study - (Full text)
 * 2021, Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - (Full text)

Learn more

 * 20 Oct 2016, The RituxME and CycloME studies – Ongoing Clinical Research in the ME/CFS Research Group
 * CycloME website
 * ClinicalTrial.gov page for CycloME study