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

NCT ID: NCT01561833

Last Updated: 2020-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2013-06-30

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.

Conditions

T Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sorafenib

Sorafenib, 400 mg PO twice daily

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francine Foss, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale Cancer Center

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

0901004690

Identifier Type: -

Identifier Source: org_study_id