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

Yale University

Status and phase

Completed

Phase 1

Conditions

T Cell Lymphoma

Treatments

Drug: Sorafenib

Study type

Interventional

Funder types

Other

Identifiers

NCT01561833

0901004690

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 patients

Sex

All

Ages

18 to 85 years old

Volunteers

Accepts Healthy Volunteers

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.