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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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T Cell Lymphoma

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib<br>Sorafenib, 400 mg PO twice daily | Drug: Sorafenib<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed or refractory T cell lymphoma