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

Primary Purpose

Cutaneous T-Cell Lymphoma, Unspecified, Chronic Graft Versus Host Disease in Skin

Status
Completed
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
ECP with 5-aminolevulinic acid
Sponsored by
St. Olavs Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cutaneous T-Cell Lymphoma, Unspecified focused on measuring Photopheresis, 5-aminolevulinic acid, Extracorporeal Circulation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St Olavs Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ALA-ECP

Arm Description

Extracorporeal photopheresis (ECP) with 5-aminolevulinic acid replacing psoralen

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
April 6, 2017
Last Updated
January 12, 2023
Sponsor
St. Olavs Hospital
Collaborators
Norwegian University of Science and Technology, Oslo University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03109353
Brief Title
Modification of Extracorporeal Photopheresis in Cutaneous T-cell Lymphoma or Chronic Graft-versus-host Disease
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
September 20, 2017 (Actual)
Primary Completion Date
December 31, 2022 (Actual)
Study Completion Date
December 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Olavs Hospital
Collaborators
Norwegian University of Science and Technology, Oslo University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cutaneous T-Cell Lymphoma, Unspecified, Chronic Graft Versus Host Disease in Skin
Keywords
Photopheresis, 5-aminolevulinic acid, Extracorporeal Circulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ALA-ECP
Arm Type
Experimental
Arm Description
Extracorporeal photopheresis (ECP) with 5-aminolevulinic acid replacing psoralen
Intervention Type
Drug
Intervention Name(s)
ECP with 5-aminolevulinic acid
Other Intervention Name(s)
5-ALA
Intervention Description
extracorporeal photopheresis (ALA-ECP) using 5-aminolevulinic acid instead of psoralen (8-MOP) in a maximum of 10 treatment cycles
Primary Outcome Measure Information:
Title
Treatment safety: Monitored through recordings of ECG, vital signs and safety laboratory measurements including haematology, clinical chemistry and urinalysis.
Description
Monitored through recordings of ECG, vital signs and safety laboratory measurements including haematology, clinical chemistry and urinalysis.
Time Frame
up to 1 year
Secondary Outcome Measure Information:
Title
Main efficacy for CTCL
Description
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.
Time Frame
up to 1 year
Title
Main efficacy for cGvHD
Description
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.
Time Frame
up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: progressive disease: disease progression from baseline in skin score, blood or lymph nodes after 3-6 months or stable disease: No- response after 3-6 months or 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 presence of at least 1 clinical sign of cGvHD or at least one distinct manifestation confirmed by pertinent biopsy or other relevant tests. 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: progression of cutaneous cGvHD defined as >25% worsening from baseline as measured by the percent change in the total skin score or 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vigleik Jessen, md
Organizational Affiliation
St Olavs Hospital, Trondheim Unversity Hospital
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Torstein Baade Rø, md phd
Organizational Affiliation
Norwegian University of Science and Technology
Official's Role
Study Director
Facility Information:
Facility Name
St Olavs Hospital
City
Trondheim
Country
Norway

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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