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A Phase I/II Study of Daily Oral Polyphenon E in Asymptomatic, Rai Stage 0-II Patients With Chronic Lymphocytic Leukemia

Phase 1/Phase 2
18 Years
Not Enrolling

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Trial Information

A Phase I/II Study of Daily Oral Polyphenon E in Asymptomatic, Rai Stage 0-II Patients With Chronic Lymphocytic Leukemia


Phase I

- Determine the maximally tolerated dose of green tea extract (Polyphenon E) in patients
with previously untreated stage 0-II chronic lymphocytic leukemia.

- Describe the dose-limiting toxicity of green tea extract (Polyphenon E).

Phase II

- Evaluate the response rate and response duration of patients with previously untreated,
asymptomatic Rai stage 0-II chronic lymphocytic leukemia treated with green tea extract
(Polyphenon E) for 6 months at the MTD.

- Further characterize toxicity.

OUTLINE: This is a phase I, dose-escalation study of green tea extract (Polyphenon E)
followed by a phase II study.

- Phase I: Patients receive oral green tea extract (Polyphenon E) once or twice daily for
4 weeks. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease
progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of green tea extract (Polyphenon E) until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 2 of 6 patients experience dose-limiting toxicity.

- Phase II: Patients receive green tea extract (Polyphenon E) as in the phase I portion
of the study at the MTD.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 73 patients will be accrued for this study.

Inclusion Criteria


- Confirmed diagnosis of chronic lymphocytic leukemia (CLL)

- Stage 0, I, or II disease

- Previously untreated disease

- Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the
diagnosis of CLL

- Absolute lymphocyte count > 10,000/mm^3

- Lymphocytosis must consist of small to moderate size lymphocytes, with ≤ 55%
prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically

- Phenotypically characterized B-CLL defined by all of the following criteria:

- A population of leukemic cells that co-expresses the B-cell antigen CD23 as
well as CD5 in the absence of other T-cell markers (CD3, CD2, etc.)

- Dim surface immunoglobulin expression

- Exclusively κ or λ light chains

- Mantle cell lymphoma must be excluded by demonstrating the absence of the
t(11:14) by FISH testing

- Patients who require chemotherapy for treatment of CLL, based on any of the following
criteria, are excluded:

- CLL-related symptoms requiring treatment, including any of the following:

- Unintentional weight loss ≥ 10% body weight within the previous 6 months

- Extreme fatigue

- Fevers > 100.5°F for 2 weeks without evidence of infection

- Night sweats without evidence of infection

- Evidence of progressive marrow failure due to CLL involvement of bone marrow as
manifested by the development of worsening anemia (hemoglobin < 11 g/dl) and/or
thrombocytopenia (platelet count < 100,000/mm^3)

- Thrombocytopenia due to immune phenomena (ITP) is permitted as long as
platelet count is ≥ 100,000/mm^3and the patient is not on active
pharmacologic therapy

- Massive (i.e. > 6 cm below left costal margin) or progressive splenomegaly

- Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive

- Progressive lymphocytosis with an increase of > 50% over 2 month period, or an
anticipated lymphocyte doubling time of < 6 months


- Platelet count ≥ 100,000/µL

- ANC ≥ 1500/µL

- Hemoglobin ≥ 11 g/dL

- Total or direct bilirubin ≤ 1.5 x upper limit of normal (ULN)

- AST (SGOT) and ALT (SGPT) ≤ 2 x ULN

- Creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 40 mL/min

- May have a history of autoimmune hemolytic anemia (AIHA) and positive Coombs test
provided there has not been active hemolysis requiring transfusion or steroid
treatment ≤ 10 weeks prior to registration

- ECOG performance status 0, 1, or 2

- Life expectancy of ≥ 6 months

- No uncontrolled infection

- No myocardial infarction within the past 6 weeks

- No New York Heart Association class III or IV congestive heart failure

- Not pregnant or nursing

- Negative pregnancy test

- Must employ adequate contraception (condoms, diaphragm, birth control pills,
injections, intrauterine device [IUD], or abstinence, etc.) prior to study entry and
for the duration of study participation

- No other severe medical or psychiatric illness

- No active hemolysis requiring transfusion or other pharmacologic therapy


- At least 8 weeks since prior and no other concurrent over the counter green tea or
green tea extract

- No prior daily use of over the counter green tea products for medicinal purposes for
> 4 weeks (phase II only)

- No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary
therapy considered investigational (utilized for a non-FDA-approved indication and in
the context of a research investigation)

- No concurrent combination anti-retroviral therapy for HIV positive patients

- No concurrent oral steroid preparations

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With a Confirmed Response [Complete Response (CR) and Partial Response (PR)] on 2 Consecutive Evaluations at Least 4 Weeks Apart

Outcome Description:

National Cancer Institute working group criteria (NCIWG) was used to assess response. CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Tait D. Shanafelt, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

August 2005

Completion Date:

August 2012

Related Keywords:

  • Leukemia
  • B-cell chronic lymphocytic leukemia
  • stage 0 chronic lymphocytic leukemia
  • stage I chronic lymphocytic leukemia
  • stage II chronic lymphocytic leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



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