Extracorporeal Photopheresis in Sezary Syndrome

Recruiting

• Conditions: Sezary Syndrome
• Interventions: Device: Extracorporeal photopheresis (ECP); Drug: Methoxsalen Injection

• Registration Number: NCT05157581
• Lead Sponsor: Oleg E. Akilov, MD, PhD

Brief Summary

The primary endpoint is to determine if ECP induces a decrease in % of tumor cells after treatment. 15 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

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.

Study Timeline

• Study First Submitted: 2021-11-16
• Study First Submitted QC: 2021-12-01
• Study First Posted: 2021-12-15
• Study Start: 2023-04-04
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-06
• Last Update Posted: 2025-01-08
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

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

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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 -

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Sezary Syndrome	Methoxsalen Injection	15 subjects with Sezary Syndrome will comprise the single arm of this study
Sezary Syndrome	Extracorporeal photopheresis (ECP)	15 subjects with Sezary Syndrome will comprise the single arm of this study

Primary Outcome Measures

Name	Time	Method
Change from baseline in tumor-specific immunity	Up to 6 months post baseline	Evaluate immune responses post ECP using innovative technology such as single-cell RNA sequencing (scRNAseq) coupled with TCR sequencing to characterize ECP-related change in malignant cells

Secondary Outcome Measures

Name	Time	Method
Change from baseline in the objective response rate for ECP therapy	Up to 6 months post baseline	.Evaluate response in skin and blood using a modified skin weighted assessment tool that assess the tumor burden in the skin and blood flow cytometry that assesses the tumor burden in the blood. If tumor burden detected internally (visceral) or in the lymph nodes at baseline, follow up CT scans will be used to evaluate lymph nodal and/or visceral response. Response rate is defined as 50% or greater decrease in skin, lymph node/visceral, or blood tumor burden

Trial Locations

Locations (1)

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States