Extracorporeal Photopheresis in Sezary Syndrome

NCT ID: NCT05157581

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

20 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-04-04

Study Completion Date

2028-12-31

Brief Summary

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The primary endpoint is to determine if ECP induces a decrease in % of tumor cells after treatment. 20 patients with Sezary Syndrome will receive ECP weekly x4, then bi-weekly for 5 months. Each patient will donate 5 samples to determine immune responses in peripheral blood. Additional clinical assessments will be a modified skin weighted assessment and flow cytometry at baseline and months 3 and 6. A CT scan will be obtained at baseline and only repeated if pathology is present at baseline. The tumor microenvironment will be studied by comparing transcriptomics of the blood samples before, 1 day after first ECP treatment, cycle 1, 1, 3 and 6 months after ECP treatment by scRNAseq (5 samples total per patient ).

Detailed Description

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Cutaneous T-cell lymphoma (CTCL) is a group of skin lymphomas in which malignant lymphocytes infiltrate the skin and, in the later stages, spread to the lymph nodes and blood (leukemia). In the early stages, CTCL generally has a slow course, but in advanced diseases, such as Sezary syndrome (the leukemic form of the disease), there is rapid deterioration. Sezary syndrome is an end-stage variant of CTCL with a mean survival of 1.5 years despite aggressive therapies. Treatment options for the advanced disease are severely limited.

In this study, informed consent will be offered to patients who are candidates for standard of care ECP and have a diagnosis of Sezary Syndrome. Participating patients will undergo ECP twice weekly for 4 weeks then twice monthly for 5 more months (month 6 of therapy). Research blood samples to assess immune responses will be obtained from a blood draw at baseline (before starting ECP), one day after first ECP, and at months 1, 3, and 6. Standard of care assessments to determine the objective response will include measurement of skin tumor burden (mSWAT), blood tumor burden (flow cytometry) and CT scan at baseline and only repeated at month 3 and 6 if lymph node or visceral (organ) involvement identified at baseline.

The investigators propose to establish changes in the tumor microenvironment after ECP, compare transcriptomic differences in malignant lymphocytes, monocytes, DC, and CD8 effectors before and after ECP to test the hypothesis that anti-tumor immune responses can be induced by ECP. We will employ a highly innovative technology such as single-cell RNA sequencing (scRNAseq) coupled with TCR sequencing to characterize ECP-related change in malignant cells utilizing a custom gene set and validate the single-cell protein data by antibody-oligo conjugates. To better understand the relevance of biomarker changes to disease progression, the observed ECP-related changes in tumor microenvironment will be correlated with clinical outcomes.

Conditions

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Sezary Syndrome

Keywords

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extracorporeal photopheresis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Sezary Syndrome

20 subjects with Sezary Syndrome will comprise the single arm of this study

Extracorporeal photopheresis (ECP)

Intervention Type DEVICE

Extracorporeal photopheresis is a process that exposes a collection of white blood cells and plasma to a light sensitizing agent, methoxsalen, and returns that compartment to the body.

Methoxsalen Injection

Intervention Type DRUG

Methoxsalen is a light-sensitizing sterile compound added to the collected white blood cells and plasma during ECP.

Interventions

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Extracorporeal photopheresis (ECP)

Extracorporeal photopheresis is a process that exposes a collection of white blood cells and plasma to a light sensitizing agent, methoxsalen, and returns that compartment to the body.

Intervention Type DEVICE

Methoxsalen Injection

Methoxsalen is a light-sensitizing sterile compound added to the collected white blood cells and plasma during ECP.

Intervention Type DRUG

Other Intervention Names

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ECP photopheresis Uvadex

Eligibility Criteria

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Inclusion Criteria

1. Patient with an established diagnosis of Sezary syndrome (stage IVA1)
2. Patients amenable for ECP
3. The patient must have a minimum wash-out period of 3 weeks between the last dose of prior systemic therapy
4. Patients should have recovered from all adverse events related to prior therapy to ≤ grade 1
5. Signed informed consent form prior to any protocol-specific procedures.

Exclusion Criteria

1. Visceral metastasis of lymphoma
2. Concomitant administration of radiotherapy or systemic anti-cancer therapy including but not restricted to: chemotherapy, biological agents, or immunotherapy
3. Patients with known NCI CTCAE grade 3 or higher active systemic or cutaneous viral, bacterial, or fungal infection.
4. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment and/or comply with study protocol.
5. Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document.
6. Patients with known allergy to Methoxsalen or heparin (as part of SOC ECP procedure).
7. Patients who are pregnant. -
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Therakos

INDUSTRY

Sponsor Role collaborator

Oleg E. Akilov, MD, PhD

OTHER

Sponsor Role lead

Responsible Party

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Oleg E. Akilov, MD, PhD

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Oleg E Akilov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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Emory University School of Medicine

Atlanta, Georgia, United States

Site Status NOT_YET_RECRUITING

Cutaneous Translational Research Program - Johns Hopkins Medicine

Baltimore, Maryland, United States

Site Status RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Charity Ruhl, LPN

Role: CONTACT

Phone: 4126472013

Email: [email protected]

Nicolena Verardi, PA-C

Role: CONTACT

Phone: 412-864-3682

Email: [email protected]

Facility Contacts

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Pamela B Allen, MD, MSc

Role: primary

Toan Bui, BS

Role: primary

Charity Ruhl, LPN

Role: primary

Nicolena Verardi, PA-C

Role: backup

References

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Ying Z, Shiue L, Park K, Kollet J, Bijani P, Goswami M, Duvic M, Ni X. Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma. Oncotarget. 2019 May 7;10(34):3183-3197. doi: 10.18632/oncotarget.26900. eCollection 2019 May 7.

Reference Type BACKGROUND
PMID: 31139332 (View on PubMed)

Zic JA. Extracorporeal Photopheresis in the Treatment of Mycosis Fungoides and Sezary Syndrome. Dermatol Clin. 2015 Oct;33(4):765-76. doi: 10.1016/j.det.2015.05.011. Epub 2015 Jul 29.

Reference Type BACKGROUND
PMID: 26433848 (View on PubMed)

Spary LK, Al-Taei S, Salimu J, Cook AD, Ager A, Watson HA, Clayton A, Staffurth J, Mason MD, Tabi Z. Enhancement of T cell responses as a result of synergy between lower doses of radiation and T cell stimulation. J Immunol. 2014 Apr 1;192(7):3101-10. doi: 10.4049/jimmunol.1302736. Epub 2014 Mar 5.

Reference Type BACKGROUND
PMID: 24600032 (View on PubMed)

Curion F, Handel AE, Attar M, Gallone G, Bowden R, Cader MZ, Clark MB. Targeted RNA sequencing enhances gene expression profiling of ultra-low input samples. RNA Biol. 2020 Dec;17(12):1741-1753. doi: 10.1080/15476286.2020.1777768. Epub 2020 Jun 28.

Reference Type BACKGROUND
PMID: 32597303 (View on PubMed)

Other Identifiers

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STUDY21100115

Identifier Type: -

Identifier Source: org_study_id