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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00262743
• Other study ID #: CDR0000454773
• Secondary ID: P30CA0150831155-
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 6, 2005
• Last updated: May 3, 2013
• Start date: August 2005
• Est. completion date: August 2012

Study information

• Verified date: May 2013
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Other known NCT identifiers

• NCT00166335

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: August 2012
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ? or ? 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

Study Design

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Biological:
• Polyphenon E
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

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Shanafelt TD, Call TG, Zent CS, LaPlant B, Bowen DA, Roos M, Secreto CR, Ghosh AK, Kabat BF, Lee MJ, Yang CS, Jelinek DF, Erlichman C, Kay NE. Phase I trial of daily oral Polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leu — View Citation

Shanafelt TD, Call TG, Zent CS, Leis JF, LaPlant B, Bowen DA, Roos M, Laumann K, Ghosh AK, Lesnick C, Lee MJ, Yang CS, Jelinek DF, Erlichman C, Kay NE. Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymp — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	24 Month Treatment Free Survival Rate	Percentage of participants who were alive and treatment (for progressive CLL) free at 24 months. The 24 month treatment free survival, with 95% CI, was estimated using the Kaplan-Meier method.	24 months (from registration)	No
Primary	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	No
Primary	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	No
Secondary	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	No