Green Tea Extract in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Green tea extract contains ingredients that may slow the growth of certain cancers. PURPOSE: This phase I/II trial is studying the side effects and best dose of green tea extract and to see how well it works in treating patients with stage 0, stage I, or stage II chronic lymphocytic leukemia (CLL).

Detailed Description
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OBJECTIVES: 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.

Official Title
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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

Conditions
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Leukemia

Intervention / Treatment
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* Biological: Polyphenon E


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: 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 adenopathy Progressive lymphocytosis with an increase of > 50% over 2 month period, or an anticipated lymphocyte doubling time of < 6 months PATIENT CHARACTERISTICS: 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 PRIOR CONCURRENT 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: polyphenon E<br>Designed to assess toxicity, treatment response, and pertinent laboratory measurements in patients with previously untreated, asymptomatic, Rai Stage 0-II CLL. | Biological: Polyphenon E<br>* Phase I Dose Escalation:. 400 mg orally twice a day to 2000 mg orally twice a day Phase II: 2000 mg orally twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Confirmed Response [Complete Response (CR) and Partial Response (PR)] on 2 Consecutive Evaluations at Least 4 Weeks Apart | 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 | 6 months | 
| Number of Participants With Biological Response (Bio-R) on 2 Consecutive Evaluations at Least 4 Weeks Apart | Bio-R: A reduction in the absolute lymphocyte count (ALC) of more than 20% from the pretreatment level for at least 2 months or a >= 30% reduction in all palpable lymphadenopathy without meeting the NCIWG criteria for PR was required | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Confirmed Complete Response (CR) | A confirmed complete response is a CR which is reported on 2 consecutive cycles at least 4 weeks apart. CR is defined in Primary Outcome Measure #1. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell chronic lymphocytic leukemia, stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia