Phase II trial of daily, oral green tea extract in patients with asymptomatic, Rai stage 0-II chronic lymphocytic leukemia (CLL).

Abstract

6522 Background: Green tea has long been touted as a health promoting substance. In vitro testing and a phase I trial suggest the green tea extract epigallocatechin 3 gallate(EGCG) may have clinical efficacy for chronic lymphocytic leukemia (CLL) patients. To follow-up on these results, we performed a phase II trial of daily EGCG in patients with CLL. Methods: Previously untreated patients with asymptomatic, Rai stage 0-II CLL and a minimum absolute lymphocyte count (ALC) ≥10 x109/L were eligible for participation. Polyphenon E with a standardized dose of EGCG (2,000 mg/dose) was administered twice daily for 6 months. Response was classified using the NCI Working Group (WG) Criteria. Results: Forty-two eligible patients received EGCG 2000 mg twice daily for up to 6 months. Patients received a median of 6 cycles of treatment (range: 1-6). Accrual to the trial is complete. Thirty-one patients have completed study therapy while 11 patients have not yet completed treatment. The most common side effects included transaminitis (31% grade 1, 12% grade 2), abdominal pain (21% grade 1, 7% grade 2, 2% grade 3), and nausea (55% grade 1, 2% grade 2). Only 2/48 (4.8%) patients experienced grade 3 toxicity. One patient experienced an NCI WG partial remission. Other signs of clinical activity were observed with 13 (31%) patients experiencing a sustained ≥ 20% reduction in ALC and 19 of 29 (66%) patients with palpable adenopathy experiencing at least a 50% reduction in the sum of the products of all nodal areas during treatment. Overall 28 (67%) patients fulfilled the criteria for a biologic response (JCO 27:3808) based on attaining either a sustained ≥ 20% decline in ALC and/or a ≥ 50% reduction in the sum of the products of all nodal areas at some point during the 6 months of active treatment. Conclusions: Daily oral EGCG in the Polyphenon E preparation was well tolerated by CLL patients in this phase II trial. Declines in ALC and/or lymphadenopathy were observed in the majority of patients. EGCG containing green tea extracts may have potential as disease stabilizing agents in patients with early-stage CLL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Genzyme, Novartis, Polyphenon E International FDA