Clinical trial NCT05157581: Extracorporeal Photopheresis in Sezary Syndrome
Official title: Open Label, Single-cohort, and Single-center Phase II Study Evaluating Tumor-specific Immunity After Extracorporeal Photopheresis in Patients with Sézary Syndrome At Single-cell Resolution
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sezary Syndrome
Keywords: extracorporeal photopheresis
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
First posted: 2021-12-15
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Sezary syndrome

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.

Eligibility criteria: 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.

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 -

Primary outcomes:
measure: Change from baseline in tumor-specific immunity
timeFrame: Up to 3 months post baseline
measure: Change from baseline in tumor-specific immunity
timeFrame: Up to 6 months post baseline
Secondary outcomes:
measure: Change from baseline in the objective response rate for ECP therapy
timeFrame: Up to 3 months post baseline
measure: Change from baseline in the objective response rate for ECP therapy
timeFrame: Up to 6 months post baseline
Other outcomes:
measure: Change from baseline in the objective response rate by disease compartment
timeFrame: Up to 3 months post baseline
measure: Change from baseline in the objective response rate by disease compartment
timeFrame: Up to 6 months post baseline
measure: Correlation of clinical responses and changes in tumor microenvironment in the blood.
timeFrame: Up to 6 months post baseline
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Oleg E Akilov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.