MethylphenIdate for Fatigue in Haematological Cancer. A Randomized, Double-blind, Placebo-controlled, CROssover Trial - the MICRO Trial

BACKGROUND Survival prognosis in haematological malignancies has improved considerably, however the frequency and impact of the most prevalent and debilitating symptoms - cancer related fatigue (CRF) - has not improved. Up to 40% of cancer patients has daily difficulties due to CRF and fatigue and weakness is affecting 2/3 of patients. In contrast to everyday fatigue CRF is defined as an unusual and persistent sense of tiredness, weakness, or even exhaustion that is not relieved by rest or sleep and leads to decreased physical or mental capacity.

Haematological cancer is often associated with fatigue due to both anemia and constitutional symptoms. Myeloablative chemotherapeutic regimens and stem cell transplantations are unique for haematological cancer treatment and these very potent regimens may result in CRF even after several years. CRF among haematological cancer patients is associated with reduced adherence to physicians recommendations [11] and permanent withdrawal from labor market. Patients express that their single most prevalent and severe problem is "dealing with feeling tired", exceeding the proportion who expresses problems "in dealing with not feeling sure that the cancer has gone" or "being told they had cancer".

An increasing emphasis has been given to rehabilitation in cancer patients and individualized exercise programs; however, these will only be feasible among a minority of haematological cancer patients. In recent years, studies using methylphenidate (MTP) in the treatment of CRF in solid cancer have been conducted, some of which have found improvements in fatigue with MTP and without significant adverse effects. These studies show that MTP may be beneficial in management of CRF. However, patients in concurrent chemotherapy were unlikely to benefit.

STUDY RATIONALE AND OBJECTIVE Patients with haematological malignancies have a severe unmet need in dealing with CRF and hardly any patients with haematological malignancies have been included in previous intervention studies. MTP treatment has been found to be safe in this setting . The current study aims at studying whether MTP can be used for management of CRF in patients with haematological cancer in order to improve also functional capacity and quality of life (QoL). Many of the patients in the current study will have no other treatment options to improve their fatigue, QoL, and functional capacity.

STUDY END-POINTS The primary end point it patient reported fatigue after six weeks of MTP treatment measured by the FACIT-F scale. A good clinical response is defined as a 25% reduction in fatigue from baseline score. Secondary end-points are changes in hours awake, in time spend at work, being social, house work / gardening, being outside, participating in exercise, in muscle strength and endurance, in QoL, and in number of blood transfusions.