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

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.

Study Overview

• Status: Completed
• Conditions: T Cell Lymphoma
• Intervention / Treatment: Drug: Sorafenib

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall response rate to sorafenib. Complete response by recist criteria was complete disappearance of all tumor lesions. partial response was 30% reduction in all sites of disease.	29 days

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Francine Foss, MD, Yale University

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: March 13, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (Estimate): March 23, 2012

Study Record Updates

• Last Update Posted (Actual): August 13, 2020
• Last Update Submitted That Met QC Criteria: August 12, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: relapsed or refractory T cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 0901004690

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO