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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00262743
First received: December 6, 2005
Last updated: May 3, 2013
Last verified: May 2013
  Purpose

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).


Condition Intervention Phase
Leukemia
Biological: Polyphenon E
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Daily Oral Polyphenon E in Asymptomatic, Rai Stage 0-II Patients With Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • 24 Month Treatment Free Survival Rate [ Time Frame: 24 months (from registration) ] [ Designated as safety issue: No ]
    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.


Enrollment: 73
Study Start Date: August 2005
Study Completion Date: August 2012
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: polyphenon E
Designed to assess toxicity, treatment response, and pertinent laboratory measurements in patients with previously untreated, asymptomatic, Rai Stage 0-II CLL.
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


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262743

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Tait D. Shanafelt, MD Mayo Clinic
Principal Investigator: Jose F Leis, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00262743     History of Changes
Obsolete Identifiers: NCT00166335
Other Study ID Numbers: CDR0000454773, P30CA015083, 1155-05, NCI-2009-01227, MC0419
Study First Received: December 6, 2005
Results First Received: December 7, 2011
Last Updated: May 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
B-cell chronic lymphocytic leukemia
stage 0 chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 01, 2014