Clinical trial NCT00262743: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Keywords: B-cell chronic lymphocytic leukemia
stage 0 chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-12-07
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With a Confirmed Response [Complete Response (CR) and Partial Response (PR)] on 2 Consecutive Evaluations at Least 4 Weeks Apart
timeFrame: 6 months
measure: Number of Participants With Biological Response (Bio-R) on 2 Consecutive Evaluations at Least 4 Weeks Apart
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants With a Confirmed Complete Response (CR)
timeFrame: 6 months
Other outcomes:
measure: 24 Month Treatment Free Survival Rate
timeFrame: 24 months (from registration)
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Tait D. Shanafelt, MD
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: Jose F Leis, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.