Sorafenib for the Treatment of Chronic Lymphocytic Leukemia (CLL)
This is a Phase 2 trial to evaluate the activity of sorafenib in relapsed or refractory CLL patients with an iwCLL-WG indication to receive therapy.
Sorafenib is an orally active multikinase inhibitor, which targets the RAF/MEK/ERK signaling pathway as well as several receptor tyrosine kinases. It is FDA approved for the treatment of hepatocellular carcinoma and renal cell carcinoma. Preclinical studies in the investigators laboratory demonstrated that sorafenib is cytotoxic to CLL cells.
The primary objective of the study is to determine the overall response rate of Sorafenib in previously treated CLL patients. All patients will receive sorafenib at 400 mg twice daily continuously for three months and then assessed for response. Responding patients may elect to continue on treatment for an additional 9 months.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Translational Study of Sorafenib for the Treatment of Chronic Lymphocytic Leukemia Patients|
- Overall Response Rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
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.
(Decrease in absolute lymphocyte count by 50%, decrease in lymphadenopathy (sum of lymph node product) by 50%, decrease in splenomegaly by 50%, or decrease in leukemia infiltration of the bone marrow by 50%.)
- To Determine the iwCLL-WG Defined Overall Response Rate (ORR) - Complete Response (CR) and Partial Responses (PR) to 3 Cycles of Sorafenib Therapy and Following the Completion of All Therapy. [ Time Frame: Two months following completion of treatment with sorafenib according to iwCLL guidelines. ] [ Designated as safety issue: No ]A response assessment must be performed 2 months following completion of therapy to document responses, including a bone marrow if in clinical response (CR) and a computed tomography (or magnetic resonance imaging scan [MRI]) if initial imaging was abnormal or physical examination inconclusive.
- Safety and Tolerability [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]Frequency, severity and relatedness of adverse events
|Study Start Date:||December 2011|
|Study Completion Date:||December 2014|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Sorafenib 400mg orally twice daily will be administered for three cycles (1 cycle = 28 days).
Sorafenib 400mg orally twice daily will be administered for three cycles (1 cycle = 28 days). Subjects without significant toxicity or progressive disease may elect to continue treatment for a total of twelve cycles.
Other Name: Nexavar
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) resistant disease.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01510756
|United States, California|
|UCSD Medical Center|
|La Jolla, California, United States, 92093|
|Principal Investigator:||Thomas J. Kipps, M.D., Ph.D.||UCSD Medical Center|