A Phase I/II Study of Oral green Tea Extract in Asymptomatic Rai Stage 0-II Patients with Chronic Lymphocytic Leukemia
Neil Kay, M.D
Mayo Clinic
Abstract:
Currently there is no cure for this very common leukemia, and despite the word "chronic" in its title, the disease is very frequently progressive. When this happens, while traditional therapies are more effective for inducing responses, this has yet to translate to cures in the majority of patients. In addition, there are frequent complications of traditional therapy in this cohort of patients including further suppression of immunity. We have defined a biochemical pathway mediated by a circulating protein designated as vascular endothelial growth factor (VEGF) secreted by CLL B cells that not only increases the leukemic B cell resistance to death but may play a role in a phenomenon designated as an "angiogenic switch." This latter feature has been strongly associated with disease progression and metastases in human solid tumors.
Happily, there are newer agents or drugs available that can interrupt this pathway and delay disease progression. We have tested several of these drugs and found one, epigallocatechin (EGCG) a major component of green tea that can kill significant numbers of leukemic B cells in at least 80 percent of CLL patients. Even more importantly, this drug has been tested in healthy volunteers and is found to be safe. The formulation is designated as polyphenon E and contains EGCG. This is now being tested at the National Cancer Institute and will be made available to us for testing.
Based on our preclinical work and the recent testing and availability of polyphenol E, we have designed a clinical trial for early stage CLL. This trial will be accompanied by correlative laboratory work designed to test two primary aspects: 1) to stratify CLL patients by risk parameters to see if responses to EGCG relate to risk and 2) to assess critical components of the VEGF pathway to see if responses induced by EGCG are associated with interruption of the pathway.