Study of Photopheresis in the Treatment of Erythrodermic MF and SS

NCT03563040 | Withdrawn Phase 2 DMC

• 2 other identifiers: EORTC-1636-CLTF2018-001685-42
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides/Sezary Syndrome

Outcome Measures

Primary Outcomes (1)

• Success rate of treatment (photopheresis)

  The primary endpoint is defined as successful use of photopheresis performed according to the study protocol based on the consensus guidelines. At 9 months time point after the initiation of photopheresis, evaluation of each patient will be performed. A patient will be declared a success with respect to the primary endpoint if she/he fulfills: 1. Patient has received the full protocol treatment 2. No progressive disease within the first 3 months after of the initiation of photopheresis. 3. No need for add-on (combination) treatment within the first 3 months after the initiation of photopheresis according to investigators decision. 4. Not experiencing any medical event (other than progressive disease) necessitating termination of photopheresis or interruption for more than 3 continuous months within the 6 months period

  From treatment start up to 9 months for each patient

Secondary Outcomes (10)

• Progression Free Survival, according to EORTC-International Society of Cutaneous Lymphoma (ISCL)-United States Cutaneous Lymphoma Consortium (USCLC) criteria

  From the first patient treatment start till 9 months as of LPI

• Best overall response rates, according to EORTC-ISCL-USCLC criteria

  From the first patient treatment start till 9 months as of LPI

• Number of treatment cycles required to obtain remission

  From the first patient treatment start till 9 months as of LPI

• Time to response (CR/PR)

  From the first patient treatment start till 9 months as of LPI

• Duration of response

  From the first patient treatment start till 9 months as of LPI

Study Arms (1)

Methoxsalen with the THERAKOS CELLEX Photopheresis System

EXPERIMENTAL

Treatment will be performed according to a predefined protocol based on the consensus guidelines in patients with MF/SS. Treatment should be administered for one year unless confirmed disease progression or unless other criteria for treatment discontinuation are met as specified in the protocol.

Drug: Methoxsalen; Device: THERAKOS CELLEX Photopheresis System

Interventions

Methoxsalen DRUG

Methoxsalen is used in conjunction with the THERAKOS CELLEX Photopheresis System. During each photopheresis treatment with methoxsalen, the dosage of methoxsalen is calculated according to the treatment volume (which is displayed on the display panel of the instrument) using the formula: Treatment volume x 0.017 ml of methoxsalen (20 µg/mL) for each treatment For example: Treatment volume = 240 mL x 0.017 = 4.1 mL of methoxsalen (20 µg/mL)

Also known as: Uvadex

Methoxsalen with the THERAKOS CELLEX Photopheresis System

THERAKOS CELLEX Photopheresis System DEVICE

Methoxsalen is used in conjunction with the THERAKOS CELLEX Photopheresis System.

Methoxsalen with the THERAKOS CELLEX Photopheresis System

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Mallinckrodt: collaborator

Study Sites (1)

UniversitaetsSpital Zurich - Division of Dermatology

Zurich, Switzerland

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Interventions

Methoxsalen

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Furocoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Robert Knobler

  Medical University Vienna - General Hospital AKH, Vienna, Austria

  STUDY CHAIR

• Franz Trautinger

  Karl Landsteiner University of Health Sciences, University Hospital of St. Poelten, St. Poelten, Austria

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2018
• First Posted: June 20, 2018
• Study Start: December 1, 2020
• Primary Completion: September 1, 2022
• Study Completion (Estimated): June 1, 2026
• Last Updated: September 8, 2021

Record last verified: 2021-08

Locations

CH (1)