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Green Tea - Phase I Trial Results at Mayo Clinic

Date: November 27, 2024

As many of you know, CLL Topics sponsored and funded the green tea clinical trial at Mayo Clinic, Rochester MN. For our more recent members, here is the link to the announcement of the first clinical trial we sponsored: Project Alpha Kick-off . At last, we have the official report on how this low impact approach worked. Attached below is the presentation that was made at the ASH 2024 conference.

This is a Phase I clinical trail and the major aim was to see if there was unacceptable toxicity associated with “EGCG” (epigallocatechin gallate), the active component of green tea. In addition to safety issues, Phase – I trials are conducted to figure out the correct dosage for the administration of the drug. This is done by gradually increasing the dose in each subsequent group of patients, starting at the lowest dose in the first group. Our green tea study recruited 33 CLL patients (early stage and chemo naïve and not needing immediate treatment for their CLL). The form of green tea extract used in the study was “Polyphenon E”, a clinical grade material supplied by the NCI. The first group of 3 patients started at 400 mg twice a day. There were 8 groups with gradually increasing amounts of Polyphenon E, the dosage ranging from 400 – 2,000 mg / twice a day. Even at the highest level, there was no dose limiting toxicity. This is excellent news on the toxicity front.

There were some low level adverse effects, such as nausea, abdominal pain, changes in liver function. But almost all of the adverse effects were Grade -1, a welcome bit of news for those of us who have considered the bleak implications of higher grade adverse effects associated with ‘real’ chemotherapy drugs. Frankly, these adverse effects are no more than I experience when I eat too much pizza at one sitting. (How many of you are old enough to remember the advertisement “I can’t believe I ate the whole thing!” – sort of like that). There was a small change of game plan in midstream: patients were originally asked to take the Polyphenon E capsules on an empty stomach, and this was later modified to taking them with food – presumably in order to make it easier on the body.

So, did green tea cure CLL? If that is what you expected / hoped from this trial, you will be disappointed. Nothing is life is that easy. What I hoped we would find is that green tea helped control the rate at which CLL grew and if we were lucky, actually helped roll back the darn clonal population. Obviously, this low key benefit would not be worth it if it was accompanied by nasty side effects. Guess what. That is exactly what was seen. The majority of patients on this trial had some roll back on their blood lymphocyte counts (see table below) and 7 out of 10 patients with swollen nodes had a 50% reduction in their node size at some point. Not bad for a material that did not cause much more than a mildly upset stomach!

So, does green tea work for every one? Does more of it work better with increasing dosage giving greater response? This is an important question. Part of doing controlled clinical trials like this is to answer questions like this. The Mayo researchers monitored EGCG levels in the blood (plasma) over time and for the different dosage groups. There was no clear indication that higher blood concentration of EGCG meant better response. Like most therapies in CLL, the response seemed to be different in different patients. Once again, the take home message is that one shoe does not fit all CLL patients, not even when we are talking about green tea extracts.

Your hard earned dollars paid for this study, whether they came from your donations to CLL Topics or as a grant from the NCI, supported by your tax dollars. Our volunteers risked their bodies to test this hypothesis. Over these several years, our members kept the faith and waited patiently for the results. This was the first clinical trial that CLL Topics sponsored and therefore close to my heart. Bottom line: this interesting study showed that for a lucky subset of our patients, green tea extract provided a way of not just holding the CLL under control but actually rolling it back with a relatively mild and tolerable side effects. I don’t know about you, but I would call these results more than a half full cup of tea. It surely would have taken a lot longer to brew these credible results without the active participation of the CLL patient community — and that should make you proud.

Be well,

Chaya
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[2047] A Phase 1 Trial of Daily Oral Green Tea Extract in Asymptomatic, Rai Stage 0-II Patients with Chronic Lymphocytic Leukemia. Session Type: Poster Session, Board #237-II

T.D. Shanafelt, S.H. Kaufmann, T.G. Call, Clive S. Zent, W. Wu, D.A. Bowen, C. Secreto, A.K. Ghosh, B. Kabat, C.S. Yang, D.F. Jelinek, C. Erlichman, Neil E. Kay Mayo Clinic, Rochester, MN; Rutgers University, Piscataway, NJ

BACKGROUND: Green tea has long been touted as a health promoting substance. The active chemical compounds in green tea are called polyphenols or catechins. Epigallocatechin gallate(EGCG) is the major catechin in green tea. We previously reported the in vitro ability of EGCG to induce apoptotic cell death in chronic lymphocytic leukemia(CLL) B-cells in vitro (Blood 104:788). After publication of our findings, clinical activity in individuals using over the counter green tea extracts were reported (Leuk Res 30:707). Based on this information, we opened a phase I/II trial of green tea extracts for patients with asymptomatic, early stage CLL in fall of 2024.

METHODS: The purpose of the phase I portion of this trial was to determine the optimal dose of EGCG in the Polyphenon E preparation for chronic daily administration and define tolerability in CLL patients. Previously untreated patients with asymptomatic, Rai stage 0-II CLL not currently meeting National Cancer Institute(NCI) Working Group(WG) Criteria for treatment were eligible for participation. Polyphenon E with a standardized dose of EGCG was obtained from NCI. The phase I portion of the trial was designed with 8 dose levels(range 400-2000 mg orally BID) using the standard 3 patient per dose level design. Patients remained on study up to 6 months. Grade 2 adverse events attributed to study treatment that did not respond to supportive care were considered dose limiting toxicity. The trial was designed to administer Polyphenon E in the fasting state. After accrual to dose levels 1 and 2, the U.S. FDA mandated all U.S. trials of Polyphenon E administer drug in the fed state. Accordingly, drug was administered in the fed state for dose levels 3-8. Trough plasma EGCG levels were measured 1 month after initiation of therapy. Response was classified using the NCI WG Criteria.

RESULTS: As of August 2024, 33 patients have been accrued to dose levels 1-8. The maximum tolerated dose(MTD) has not been reached. Side effects have generally been mild. The most common toxicities were nausea(grade 1: 42%; grade 2: 3%), elevation in SGOT (42%; all grade 1), and abdominal pain (36%; all grade 1). To date, no patient has had a sustained 50% reduction in both absolute lymphocyte count (ALC) and lymphadenopathy that would meet the NCI WG criteria for partial response. A majority of patients have had a reduction in ALC(Table). Among the 10 patients who had palpable adenopathy at study enrollment, 7 patients experienced at least a 50% reduction in the sum of the products of all nodal areas at some point during treatment. Trough plasma EGCG levels after 1 month of treatment ranged from 2.93974 ng/mL(median 40.5 ng/mL). Plasma levels did not clearly relate to the degree of reduction in ALC suggesting sensitivity to Polyphenon E may relate more to characteristics of the leukemic clone than plasma EGCG levels.

CONCLUSION: Daily oral EGCG in the Polyphenon E preparation was well tolerated by CLL patients in this phase I trial. The MTD has not been reached. As classified by the NCI WG criteria, no partial or complete remissions have been observed to date, however declines in ALC and lymphadenopathy have been observed in the majority of patients. The phase II portion of this trial will open at Mayo Clinic Fall 2024.

Abstract #2047 appears in Blood, Volume 110, issue 11, November 16, 2024

Keywords: B-Cell Chronic Lymphocytic Leukemia|Treatment|B-CLL

Sunday, December 9, 2024 6:00 PM

Session Info: Poster Session: CLL: Frontline Therapies and Vaccine Strategies.
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