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

Phase 1

Completed

• Conditions: T Cell Lymphoma
• Interventions: Drug: Sorafenib

• Registration Number: NCT01561833
• Lead Sponsor: Yale University

Brief Summary

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.

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 Timeline

• Study Start: 2009-10
• Study First Submitted: 2012-03-13
• Study First Submitted QC: 2012-03-21
• Study First Posted: 2012-03-23
• Primary Completion: 2013-05
• Study Completion: 2013-06
• Results First Submitted: 2016-06-15
• Status Verified: 2020-03
• Results First Submitted QC: 2020-08-12
• Last Update Submitted: 2020-08-12
• Results First Posted: 2020-08-13
• Last Update Posted: 2020-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sorafenib	Sorafenib	Sorafenib, 400 mg PO twice daily

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	29 days	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.

Trial Locations

Locations (1)

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States