Modification of Extracorporeal Photopheresis in Cutaneous T-cell Lymphoma or Chronic Graft-versus-host Disease

Modification of Extracorporeal Photopheresis Technology With 5-aminolevulinic Acid in Patients With Cutaneous T-cell Lymphoma or Chronic Graft-versus-host Disease - A Proof-of-concept Study

Extracorporeal photopheresis (ECP), is commonly used for the treatment of cutaneous T-cell lymphoma (CTCL) and chronic graft-versus-host disease. ECP (cGVHD) is an immune modulating treatment. White blood cells from the patient are standardized activated by a photosensitizer psoralen (8-MOP) and irradiated with visible ultraviolet light (UV-A). The purpose is to induce programmed cell death (apoptosis). Disadvantage of current treatment is that 8-MOP targets both diseased and normal cells with no selectivity.

The purpose of this study is to improve the current ECP technology using aminolevulinic acid (ALA) and UV light. ECP will be carried out in conventional manner except that 8-MOP will be replaced with ALA. Systemic ALA / UV light is already approved and used in the detection and treatment of disease in humans. The primary objective is to assess its safety and tolerability after single and multiple treatment in patients with CTCL or cGvHD.

Study Overview

• Status: Completed
• Conditions: Cutaneous T-Cell Lymphoma, Unspecified; Chronic Graft Versus Host Disease in Skin
• Intervention / Treatment: Drug: ECP with 5-aminolevulinic acid

Detailed Description

The main advantages of using ALA for ECP are (1) highly effective and selective apoptotic destruction of transformed/activated hyper-proliferative T-cells through an endogenously selective production of the potent photosensitiser, protoporphyrin IX (PpIX) from ALA via heme biosynthetic pathway; (2) ALA/PpIX only targets membranous structures outside of the cell nucleus thus causing no risk of carcinogenesis and (3) induces systemic anti-tumour immunity.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway
    • St Olavs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent
• cutaneous T-cell lymphoma (CTCL) (Mycosis fungoides and Sézary syndrome)

• considered to respond inadequately to 8-MOP-ECP therapy. Inadequate response is defined as:

  1. progressive disease: disease progression from baseline in skin score, blood or lymph nodes after 3-6 months or
  2. stable disease: No- response after 3-6 months or
  3. minimal response < 50% (from baseline) reduction of skin scores and/or CD4/CD8 ratio or a loss of peripheral blood clone after 3-6 months.

• (or) chronic graft-versus-host disease (cGvHD) and considered to respond inadequately to 8-MOP-ECP therapy. Chronic GvHD is defined as

  1. presence of at least 1 clinical sign of cGvHD or
  2. at least one distinct manifestation confirmed by pertinent biopsy or other relevant tests.
  3. steroid dependence, intolerance or steroid refractoriness considered to respond inadequately to 8-MOP-ECP therapy with at least monthly intervals.

Inadequate response is defined as:

1. progression of cutaneous cGvHD defined as >25% worsening from baseline as measured by the percent change in the total skin score or
2. after 3 months had an inadequate response of cutaneous cGvHD as defined by <15% improvement in the total skin score compared with baseline, or a ≤25% reduction in corticosteroid dose.

Exclusion Criteria:

• Photosensitive comorbidities, porphyria or known hypersensitivity to 5-aminolevulinic acid or porphyrins
• Aphakia
• Pregnancy or breast feeding. (A negative urine pregnancy test must be demonstrated in female patients of child-bearing potential at the Screening Visit)
• Ongoing cardiac and pulmonary diseases or ASAT, ALAT, Bilirubin or INR value ≥ 3x upper limit of normal or clinically significant ECG findings
• Polyneuropathy
• Uncontrolled infection or fever
• History of heparin-induced thrombocytopenia, absolute neutrophil count <1x10-9 L-, platelet count <20x10-9 L-1
• Body weight below 40 kg
• Investigator considers subject unlikely to comply with study procedures, restrictions and requirements.
• History of any clinically significant disease or disorder which in the opinion of the investigator, may either put the patient at risk because of participation in the study, or influence the result or the patient's ability to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALA-ECP; Extracorporeal photopheresis (ECP) with 5-aminolevulinic acid replacing psoralen	Drug: ECP with 5-aminolevulinic acid; extracorporeal photopheresis (ALA-ECP) using 5-aminolevulinic acid instead of psoralen (8-MOP) in a maximum of 10 treatment cycles; Other Names: 5-ALA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment safety: Monitored through recordings of ECG, vital signs and safety laboratory measurements including haematology, clinical chemistry and urinalysis.	Monitored through recordings of ECG, vital signs and safety laboratory measurements including haematology, clinical chemistry and urinalysis.	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main efficacy for CTCL	Response of skin disease and reduction in immunosuppression. Response will be evaluated with study baseline as reference as: complete response, partial response, minimal response, stable disease, progressive disease or maximal response based on set definitions.	up to 1 year
Main efficacy for cGvHD	Response of skin disease and reduction in immunosuppression. Response will be evaluated with study baseline as reference as: complete response, partial response, minimal response, stable disease, progressive disease or maximal response based on set definitions.	up to 1 year

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: Oslo University Hospital; Norwegian University of Science and Technology
• Investigators: Study Director: Vigleik Jessen, md, St Olavs Hospital, Trondheim Unversity Hospital; Study Director: Torstein Baade Rø, md phd, Norwegian University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: April 6, 2017
• First Submitted That Met QC Criteria: April 11, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Photopheresis; 5-aminolevulinic acid; Extracorporeal Circulation
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Graft vs Host Disease; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: 2016-000872-78 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No