A Phase II Translational Study of Sorafenib for the Treatment of Chronic Lymphocytic Leukemia Patients
The UCSD Moores Cancer is conducting a Phase 2 clinical trial to evaluate the activity of
sorafenib in relapsed or refractory CLL patients.
Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor with effects on tumor
proliferation and tumor angiogenesis. It was initially selected based on inhibition of the
serine/threonine kinases Raf-1 and wild-type B-Raf, which are pivotal components of the
Ras/Raf/MEK/ERK signaling pathway. CLL cells derive survival support from their
microenvironment, in part by activation of this pathway. Preclinical studies performed in
our lab demonstrated that sorafenib was cytotoxic to CLL cells, including those from
patients with more aggressive disease and from patients with chemotherapy (fludarabine)
The purpose of this study is to evaluate for evidence of anti-leukemic activity / clinical
activity of sorafenib by assessing decrease in absolute lymphocyte count (ALC)/leukemia cell
counts, lymphadenopathy, splenomegaly, and leukemia infiltration of bone marrow and to
assess the impact of sorafenib on the CLL B cells through corollary studies. Patients will
continue treatment for up to 3 monthly cycles unless toxicity or progressive disease.
Patients with noted stable disease (or better) in the absence of significant toxicity will
be allowed to receive another 1-9 cycles of single agent sorafenib. All patients will be
assessed for response following 3 cycles of treatment and/or following all therapy per
iwCLL-WG 2008 guidelines.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall response rate
Determination of absolute lymphocyte count (ALC), lymphadenopathy, splenomegaly, and/or marrow leukemia as measured by 4-color flow MRD panel after 3 cycles of study treatment
Thomas J. Kipps, M.D., Ph.D.
UCSD Medical Center
United States: Institutional Review Board
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