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

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.

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