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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01561833
First received: March 13, 2012
Last updated: September 4, 2013
Last verified: September 2013
  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:


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.


Enrollment: 15
Study Start Date: October 2009
Study Completion Date: June 2013
Primary Completion Date: May 2013 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06510
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: September 4, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
relapsed or refractory T cell lymphoma

Additional relevant MeSH terms:
Lymphoma, T-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014