Lack of feasibility

PROMPT: a study of photopheresis for the treatment of erythrodermic mycosis fungoides and Sézary syndrome

For this study, the investigators invite patients suffering from erythrodermic mycosis fungoides (MF) and Sézary syndrome (SS) whose skin symptoms have not responded to other types of treatment prescribed by their doctors (symptoms came back or got worse) as well as patients that never received any treatment.

Patients will be treated with photopheresis every two weeks for the first three months, thereafter once monthly. One treatment cycle consists of 2 day treatment in a row. After 6 months of treatment, treatment can be given every 5 to 8 weeks.

During the photopheresis procedure, the patient's blood is collected into a specialized machine (THERAKOS CELLEX) that separates the white blood cells from the other blood components. The other blood components are returned to the patient and white blood cells are then treated with the drug methoxsalen, which makes them sensitive to ultraviolet light. The treated white blood cells are exposed to ultraviolet A (UVA) irradiation inside the machine, and then returned to the patient.

As photopheresis has been used worldwide for more than 30 years, each hospital has developed their own guidelines (e.g. which patients, frequency, etc). Recently, experts in the field have developed a guidance which will now be tested in this study.

Inclusion criteria:

• Erythrodermic mycosis fungoides or Sézary Syndrome (T4, N0-3, M0, B0-2) (for staging see table 1)
• World Health Organization (WHO) performance status (PS) 0-2
• Any prior treatment
• With the exception of topical corticosteroids, skin care, itch and pain relieves all prior therapies for MF/SS have to be stopped/completed before registration.
• No specific wash out period prior to registration is defined
• Age ≥ 18, no upper limit
• Measurable disease
• Adequate bone marrow function at time of registration :
• Hemoglobin > 9.0 g/dL (> 5.6 mmol/L);
• White blood cell count > 1 x 109/L (> 1000/mm3) and < 25 x 109/L (< 25,000/mm3);
• Platelet count > 20 x 109/L (> 20,000/mm3);
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) according to Modification of Diet in Renal Disease (MDRD) ≥ 50 mL/min
• Serum albumin ≥ 2.8 g/dL.
• Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to the initiation of the first study treatment.
• WOCBP should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 1 month after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable).
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomised partner
• Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
• Male patients with pregnant or non-pregnant WOCBP partner should use condom during the study treatment period and for at least 1 month after the last study treatment.
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 1 month after the last study treatment.
• Before patient registration, written informed consent must be obtained according to international conference on harmonisation/Good clinical practice (ICH/GCP) and national/local regulations.

Exclusion criteria

• History of congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe)
• History of any of the following cardiovascular conditions within 6 months prior to registration:
• Unstable angina.
• Clinically significant cardiac arrhythmias.
• Myocardial infarction.
• Poorly controlled hypertension defined at baseline as blood pressure (BP) >150/100 mmHg despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• Active cancer other than MF/SS. Exceptions:
• Patients with actinic keratoses should not be excluded, treatment should be decided by the treating physician according to local standards of care and be documented in the case report forms (CRFs)
• Patients with non-skin in situ tumors (e.g. mucosal of any site, breast,,…) should be adequately treated prior to study entry.
• Need for any systemic cancer therapy other than ECP at the time of registration according to the treating physician's decision
• History of idiosyncratic or hypersensitivity reaction to methoxsalen, psoralen compounds or any of the excipients
• Aphakia
• History of photosensitive disease like but not limited to porphyria, systemic lupus erythematosus, or albinism.
• Any medical conditions that do not allow extracorporeal volume loss like but not limited to severe cardiac disease, severe anaemia, severe renal disorder
• Previous splenectomy
• Coagulation disorders
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule