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

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Polyphenon E
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring B-cell chronic lymphocytic leukemia, stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Arizona
  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

polyphenon E

Arm Description

Designed to assess toxicity, treatment response, and pertinent laboratory measurements in patients with previously untreated, asymptomatic, Rai Stage 0-II CLL.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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.

Full Information

First Posted
December 6, 2005
Last Updated
May 3, 2013
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00262743
Brief Title
Green Tea Extract in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia
Official Title
A Phase I/II Study of Daily Oral Polyphenon E in Asymptomatic, Rai Stage 0-II Patients With Chronic Lymphocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
B-cell chronic lymphocytic leukemia, stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
polyphenon E
Arm Type
Experimental
Arm Description
Designed to assess toxicity, treatment response, and pertinent laboratory measurements in patients with previously untreated, asymptomatic, Rai Stage 0-II CLL.
Intervention Type
Biological
Intervention Name(s)
Polyphenon E
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of Participants With a Confirmed Response [Complete Response (CR) and Partial Response (PR)] on 2 Consecutive Evaluations at Least 4 Weeks Apart
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
Time Frame
6 months
Title
Number of Participants With Biological Response (Bio-R) on 2 Consecutive Evaluations at Least 4 Weeks Apart
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Number of Participants With a Confirmed Complete Response (CR)
Description
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.
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
24 Month Treatment Free Survival Rate
Description
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.
Time Frame
24 months (from registration)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tait D. Shanafelt, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jose F Leis, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19470922
Citation
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 leukemia. J Clin Oncol. 2009 Aug 10;27(23):3808-14. doi: 10.1200/JCO.2008.21.1284. Epub 2009 May 26.
Results Reference
result
PubMed Identifier
22760587
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 lymphocytic leukemia. Cancer. 2013 Jan 15;119(2):363-70. doi: 10.1002/cncr.27719. Epub 2012 Jul 3.
Results Reference
result

Learn more about this trial

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

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