A Pilot Study of Sorafenib Examining Biomarkers in Refractory or Relapsed T-Cell Lymphoma Patients - Full Text View

Purpose

This study will be a pilot study of sorafenib 400mg PO twice daily in refractory T-cell lymphomas including peripheral T-cell lymphoma (PTCL), angioimmunoblastic lymphadenopathy (AILD), cutaneous T cell lymphoma (CTCL), anaplastic large cell lymphoma (ALCL) and other transformed T-cell lymphomas with the primary objective of studying the biological effects of the multikinase inhibitor, sorafenib.

Condition	Intervention
T Cell Lymphoma	Drug: Sorafenib

Study Type:	Interventional
Study Design:	Endpoint Classification: Bio-availability Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Pilot Study of Sorafenib Examining Biomarkers in Refractory or Relapsed T-Cell Lymphoma Patients

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:

Biological Effects of Sorafenib on ERK phosphorylation in patients with T-cell lymphoma [ Time Frame: 29 days to the baseline value ] [ Designated as safety issue: No ]
A paired t-test will be used to compare the actual values if these appear to be normally distributed. Otherwise a nonparametric sign test will be used, treating the difference of every patient's baseline to their day 29 value as a toss of a fair coin.

Secondary Outcome Measures:

Objective response rate of patients following initial treatment with sorafenib and progression free survival [ Time Frame: 8 weeks following initial treatment ] [ Designated as safety issue: No ]
Patients with stable disease (SD), complete or partial response (CRIPR) lasting at least 8 weeks would be considered to have a meaningful clinical effect from sorafenib.

Estimated Enrollment:	14
Study Start Date:	October 2009
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sorafenib Sorafenib, 400 mg PO twice daily	Drug: Sorafenib Intrapatient dose reduction to 400 mg once daily and then 400 mg every other day will be allowed depending on the type and severity of toxicity encountered provided that criteria for patient withdrawal from study treatment have not been met.

Detailed Description:

Primary objectives:

• To study the biological effects of sorafenib 400mg BID on the mitogen-activated protein kinase (MAPK) pathway, specifically the inhibition of extracellular signal-regulated kinases (ERK) phosphorylation, and to correlate with clinical activity in patients with T-cell lymphoma.

Secondary objectives:

To observe the clinical activity of sorafenib 400mg BID by determining response rate, and progression free survival in patients with T-cell lymphoma. Duration of response and duration of stable disease will also be measured.
To determine the tolerability of sorafenib in patients with T-cell lymphoma.

Exploratory objectives:

To observe the effects of sorafenib on T-cell subsets (CD4/CD8 ratio, and Tregs), and the effects of sorafenib on the monocytoid population.
To observe the effects of sorafenib on the serum cytokine profile.
To observe the effects of sorafenib on the T-cell receptor pathway, i.e. Lck, ZAP-70, and Syk.
To observe changes in lymph node or skin morphology including tumor cell infiltrate, vasculature, and the tumor microenvironment in patients treated with sorafenib by performing serial biopsies of lymph nodes or skin.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Histologically confirmed T-cell lymphoma including PTCL, AITL, CTCL, ALCL (Alk+, and Alk-), and other transformed T-cell lymphomas
Age > 18 years old
Measureable disease, as defined by the Cheson criteria
ECOG Performance Status of 0 or 1
Life expectancy > 12 weeks
Adequate bone marrow, liver and renal function
Patients with hemoglobin < 8.5g/dL, or ANC 500-1000/mm3, or platelets 50,000-75,000/mm3 (Grade 3), whose cytopenias are due to bone marrow involvement by T-cell lymphoma will also be eligible

Exclusion Criteria:

Prior treatment with sorafenib, or other agents with similar activity, i.e. bevacizumab, imatinib, sunitinib.
Prior treatment with allogeneic stem cell transplant
Cardiac disease: Congestive heart failure > class II NYHA.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01561833

Contacts

Contact: Francine Foss, MD	203-737-5312	francine.foss@yale.edu
Contact: Molly Daley	203-785-2068	molly.daley@yale.edu

Locations

United States, Connecticut
Yale Cancer Center	Recruiting
New Haven, Connecticut, United States, 06510
Contact: Molly Daley 203-785-2058 molly.daley@yale.edu
Principal Investigator: Francine Foss, M.D.

Sponsors and Collaborators

Yale University

Investigators

Principal Investigator:

Francine Foss, MD

Yale University

More Information

No publications provided

Responsible Party:	Yale University
ClinicalTrials.gov Identifier:	NCT01561833 History of Changes
Other Study ID Numbers:	0901004690
Study First Received:	March 13, 2012
Last Updated:	March 21, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Yale University:

relapsed or refractory T cell lymphoma

Additional relevant MeSH terms:

Lymphoma
Lymphoma, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

Lymphoma, Non-Hodgkin
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013