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

This study is currently recruiting participants.
Verified March 2013 by New York University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Swati Goel, New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01663571
First received: August 9, 2012
Last updated: March 6, 2013
Last verified: March 2013
  Purpose

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.


Condition
Cutaneous T Cell Lymphoma

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: STAT3 in T Cells: At The Crossroads of Inflammation and Cancer

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Measure the levels of Th 17 cytokines namely Il-17 and Il-22 in CTCL [ Time Frame: 2 -3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Identify STAT3 mutations in CTCL [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

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. The investigators will assay the mRNA levels of the transcription factors of the different T effector cells by qPCR.


Estimated Enrollment: 100
Study Start Date: May 2012
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with Cutaneous T cell Lymphoma (CTCL), either newly diagnosed or with progression of disease. Patients with Eczema, psoriasis and dermatitis are also eligible for the study

Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01663571

Contacts
Contact: Swati Goel, MD 212 263 6485 swati.goel@nyumc.org

Locations
United States, New York
NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact: Swati Goel, MD    212-263-6485    swati.goel@nyumc.org   
Principal Investigator: Swati Goel, MD         
Sponsors and Collaborators
New York University School of Medicine
Investigators
Principal Investigator: Sergei Koralov, PhD NYU School of Medicine
  More Information

No publications provided

Responsible Party: Swati Goel, Hematology Oncology Fellow, New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01663571     History of Changes
Other Study ID Numbers: 11-01293
Study First Received: August 9, 2012
Last Updated: March 6, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Inflammation
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on April 17, 2014