STAT3 in T Cells: At The Crossroads of Inflammation and Cancer

Cutaneous T Cell Lymphoma Clinical Trial

Official title:

STAT3 in T Cells: At The Crossroads of Inflammation and Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01663571
• Other study ID #: 11-01293
• Status: Terminated
• Start date: May 1, 2012
• Est. completion date: November 21, 2016

Study information

• Verified date: September 2018
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Protocol Summary

Constitutive STAT3 activity is implicated in many malignancies including Cutaneous T Cell Lymphoma. It is also essential for Th17 differentiation, a subset of CD4 effector T cell, implicated in chronic inflammatory conditions and possibly CTCL. HDAC inhibitors have shown activity in CTCL but their exact mechanism of action is not known. It is known that HDAC inhibitors regulate STAT3 transcriptional activity and hence can potentially be active in CTCL through modulation of the STAT3 pathway. The hypothesis is that Th17 cytokines contribute to the initiation of cancer by creating a pro-inflammatory microenvironment that predisposes cells to neoplastic transformation. To probe this, the investigators will compare the differences in cytokine production and gene expression in the skin resident T cells from patients with benign dermatoses and CTCL as well as in the blood/circulating lymphocytes of healthy donors and Sezary syndrome (SS). The investigators will also investigate whether HDAC inhibitors have a direct impact on the number of Th17 cells, the cytokine production by these cells and phosphorylated STAT3 protein in CTCL with subsequent treatment cycles.

The objectives of this study are 1. Observe the epigenetic, transcriptional and phenotypic changes that take place in T cell during malignant transformation 2. Understand the mechanism of action of HDAC inhibitors in CTCL.

Methods: Skin biopsy specimens from cutaneous T cell lymphoma (CTCL) patients and benign skin conditions namely eczema, dermatitis and psoriasis will be obtained through a standard punch biopsy procedure from the skin lesion.

Additionally, 15 ml of peripheral blood from CTCL patients who have Sezary syndrome (SS) and from patients with benign skin condition will be collected.

CTCL patients, who are starting treatment with HDAC Inhibitors namely Vorinostat and Romidepsin, will have a total of 3 skin biopsies and/or blood draws. The first procedure would be before starting treatment with either of these HDAC inhibitors. Two more skin biopsies and/or blood draws will be performed after first and second cycle of treatment.

Levels of Th17 cytokines, IL-17, IL -22 and pSTAT3 protein will be determined by IHC staining in the skin and cytokine levels in the blood will be assayed by sandwich ELISA method.The investigators will also assay the mRNA levels of the transcription factors of the different T effector cells by qPCR.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: November 21, 2016
• Est. primary completion date: November 21, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients with CTCL that are starting new form of treatment and adult patients with benign dermatoses.

Exclusion Criteria:

• patients with lymphomas other than CTCL or leukemia

Related Conditions & MeSH terms

• Cutaneous T Cell Lymphoma
• Inflammation
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous

Locations

Country	Name	City	State
United States	NYU Langone Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
New York University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure the levels of Th 17 cytokines namely Il-17 and Il-22 in CTCL		2 -3 years
Secondary	Identify STAT3 mutations in CTCL		2-3 years