Green Tea Extract in Treating Patients With Monoclonal Gammopathy of Undetermined Significance and/or Smoldering Multiple Myeloma

Sponsor
Barbara Ann Karmanos Cancer Institute (Other)
Overall Status
Terminated
CT.gov ID
NCT00942422
Collaborator
National Cancer Institute (NCI) (NIH)
8
1
1
28
0.3

Study Details

Study Description

Brief Summary

RATIONALE: Green tea extract contains ingredients that may prevent or slow the growth of monoclonal gammopathy of undetermined significance and/or smoldering multiple myeloma.

PURPOSE: This phase II trial is studying how well green tea extract works in treating patients with monoclonal gammopathy of undetermined significance and/or smoldering multiple myeloma.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: defined green tea catechin extract
  • Genetic: gene expression analysis
  • Genetic: protein analysis
  • Other: laboratory biomarker analysis
Phase 2

Detailed Description

OBJECTIVES:

Primary

  • Conduct a pilot study investigating the effects of Polyphenon E, a compound extracted from green tea which contains epigallocatechin-3-gallate (EGCG), on monoclonal protein levels in patients with monoclonal gammopathy of undetermined significance and/or smoldering multiple myeloma.

Secondary

  • Collect, process, and store blood and marrow specimens for future measurement of the biologic effects of Polyphenon E on the plasma cells of these patients by utilizing proteosome activity assays and gene expression profiling.

OUTLINE: Patients receive oral green tea catechin extract (Polyphenon E) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood, urine, and bone marrow sample collection periodically for correlative laboratory studies. Samples are analyzed for monoclonal protein (M-protein) levels, proteosome function, and gene expression.

Study Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Clinical and Biologic Evaluation of Polyphenon E, an Extract of Green Tea Containing EGCG, in Plasma Cell Dyscrasias - Pilot Study
Study Start Date :
Nov 1, 2009
Actual Primary Completion Date :
Mar 1, 2012
Actual Study Completion Date :
Mar 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: defined green tea catechin extract / correlative analysis

Polyphenon E, an oral capsule form of EGCG extracted from green tea, 800 mg administered daily on an empty stomach (at least 1 hour before or 2 hrs after a meal)Patients receive oral green tea catechin extract (Polyphenon E) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Dietary Supplement: defined green tea catechin extract
Polyphenon E, an oral capsule form of EGCG extracted from green tea, 800 mg administered daily on an empty stomach (at least 1 hour before or 2 hrs after a meal)Patients receive oral green tea catechin extract (Polyphenon E) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Genetic: gene expression analysis
Blood and bone marrow samples will be obtained prior to the start of treatment and at the conclusion of the study for correlative studies. An additional peripheral blood sample will be obtained on day 8 of the first cycle of therapy.

Genetic: protein analysis
Blood and bone marrow samples will be obtained prior to the start of treatment and at the conclusion of the study for correlative studies. An additional peripheral blood sample will be obtained on day 8 of the first cycle of therapy.

Other: laboratory biomarker analysis
Blood and bone marrow samples will be obtained prior to the start of treatment and at the conclusion of the study for correlative studies. An additional peripheral blood sample will be obtained on day 8 of the first cycle of therapy.

Outcome Measures

Primary Outcome Measures

  1. Sustained M-protein Reduction of ≥ 25% From Baseline [Day one of each 28-day cycle for a total of up to 6 cycles]

    This is a monthly blood test, done at the beginning of each cycle of therapy. The M-protein is a surrogate marker routinely used to estimate the degree of plasma cell cyto-reduction brought about by therapy. In active multiple myeloma, a 25% reduction in the M-protein level would correspond to a "minor response," an improvement recognized as having some clinical benefit.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Measurable monoclonal protein in the serum (for immunoglobin [Ig]G or IgM, >= 1.0 g/dL using serum protein electrophoresis [SPEP]/immunofixation electrophoresis [IFE]; for IgA, an SPEP/IFE confirming the presence of a monoclonal IgA band plus a quantitative IgA level of >= 750 mg/dL) OR measurable urine Bence Jones paraprotein (>= 500mg/24hrs) OR a measurable serum free light chain (FLC), defined as an involved FLC level of >10 mg/dl, and a serum FLC ratio that is abnormal

  • Neutrophil count >= 1,500

  • Platelet count >= 100,000

  • Hemoglobin >= 9mg/dL

  • Alanine aminotransferase (ALT) =< institutional upper limit of normal (IULN)

  • Aspartate aminotransferase (AST) =< IULN

  • Total bilirubin =< IULN

  • Alkaline phosphatase =< IULN

  • Any ethnic group

  • Prior therapy is allowed if >= 4 weeks prior to registration

  • Life expectancy of at least 6 months

  • Ability to understand and the willingness to sign a written informed consent document

  • Willingness to comply with oral home treatment and visit schedule

  • Patients with reproductive capacity must be willing to use adequate contraception (barrier contraception, birth control pills, or other highly effective hormonal agents) or abstain from sexual activity for the duration of the study and 30 days beyond the end of therapy

Exclusion Criteria:
  • Pregnant women

  • Breastfeeding women

  • Confirmed symptomatic multiple myeloma (MM), defined by any of the following:

  • Lytic lesions on skeletal survey

  • Anemia attributable to plasma cell infiltrate in marrow

  • Hypercalcemia

  • Renal dysfunction not attributable to other causes

  • Uncontrolled intercurrent illness, including but not limited to active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social situations that would compromise compliance with study medication or follow up visits

  • Patients with high predisposition to gastrointestinal bleeding, such as known gastroesophageal varices or active peptic ulcer disease

  • Patients with chronic liver disease (such as hepatitis B, hepatitis C, or alcoholic cirrhosis)

  • Prior daily ingestion of green tea or green tea extract within 6 months of study entry

  • Patients who have previously experienced any adverse symptoms related to green tea or any of the inactive components present in Polyphenon E capsules

  • Concurrent use of investigational or commercial agent or therapy with the intent to treat MGUS and/or SMM

Contacts and Locations

Locations

Site City State Country Postal Code
1 Barbara Ann Karmanos Cancer Institute Detroit Michigan United States 48201

Sponsors and Collaborators

  • Barbara Ann Karmanos Cancer Institute
  • National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jeffrey A. Zonder, MD, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jeffrey Zonder, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00942422
Other Study ID Numbers:
  • CDR0000646899
  • P30CA022453
  • WSU-2009-015
  • NCT01589887
First Posted:
Jul 20, 2009
Last Update Posted:
Mar 27, 2015
Last Verified:
Mar 1, 2015

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Defined Green Tea Catechin Extract / Correlative Analysis
Arm/Group Description Polyphenon E, an oral capsule form of EGCG extracted from green tea, 800 mg administered daily on an empty stomach (at least 1 hour before or 2 hrs after a meal)Patients receive oral green tea catechin extract (Polyphenon E) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED 8
COMPLETED 5
NOT COMPLETED 3

Baseline Characteristics

Arm/Group Title Defined Green Tea Catechin Extract / Correlative Analysis
Arm/Group Description Polyphenon E, an oral capsule form of EGCG extracted from green tea, 800 mg administered daily on an empty stomach (at least 1 hour before or 2 hrs after a meal). Patients receive oral green tea catechin extract (Polyphenon E) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Participants 8
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
5
62.5%
>=65 years
3
37.5%
Sex: Female, Male (Count of Participants)
Female
4
50%
Male
4
50%
Region of Enrollment (participants) [Number]
United States
8
100%

Outcome Measures

1. Primary Outcome
Title Sustained M-protein Reduction of ≥ 25% From Baseline
Description This is a monthly blood test, done at the beginning of each cycle of therapy. The M-protein is a surrogate marker routinely used to estimate the degree of plasma cell cyto-reduction brought about by therapy. In active multiple myeloma, a 25% reduction in the M-protein level would correspond to a "minor response," an improvement recognized as having some clinical benefit.
Time Frame Day one of each 28-day cycle for a total of up to 6 cycles

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Defined Green Tea Catechin Extract / Correlative Analysis
Arm/Group Description Polyphenon E, an oral capsule form of EGCG extracted from green tea, 800 mg administered daily on an empty stomach (at least 1 hour before or 2 hrs after a meal)Patients receive oral green tea catechin extract (Polyphenon E) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. defined green tea catechin extract: Polyphenon E, an oral capsule form of EGCG extracted from green tea, 800 mg administered daily on an empty stomach (at least 1 hour before or 2 hrs after a meal)Patients receive oral green tea catechin extract (Polyphenon E) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. gene expression analysis: Blood and bone marrow samples will be obtained prior to the start of treatment and at the conclusion of the study for correlative studies. An additional peripheral blood sample will be obtained on day 8 of the
Measure Participants 8
Number [percentage of patients]
0

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group Title Defined Green Tea Catechin Extract / Correlative Analysis
Arm/Group Description Polyphenon E, an oral capsule form of EGCG extracted from green tea, 800 mg administered daily on an empty stomach (at least 1 hour before or 2 hrs after a meal)Patients receive oral green tea catechin extract (Polyphenon E) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. gene expression analysis: Blood and bone marrow samples will be obtained prior to the start of treatment and at the conclusion of the study for correlative studies. An additional peripheral blood sample will be obtained on day 8 of the
All Cause Mortality
Defined Green Tea Catechin Extract / Correlative Analysis
Affected / at Risk (%) # Events
Total / (NaN)
Serious Adverse Events
Defined Green Tea Catechin Extract / Correlative Analysis
Affected / at Risk (%) # Events
Total 1/8 (12.5%)
Metabolism and nutrition disorders
Hyperglycemia 1/8 (12.5%)
Other (Not Including Serious) Adverse Events
Defined Green Tea Catechin Extract / Correlative Analysis
Affected / at Risk (%) # Events
Total 8/8 (100%)
Blood and lymphatic system disorders
Neutropenia 3/8 (37.5%) 3
Leukopenia 3/8 (37.5%) 3
Lymphopenia 4/8 (50%) 4
Thrombocytopenia 1/8 (12.5%) 1
Cardiac disorders
Heart Palpitation 1/8 (12.5%) 1
Borderline bradycardia 1/8 (12.5%) 1
Gastrointestinal disorders
Nausea 4/8 (50%) 4
Reflux 1/8 (12.5%) 1
Loose Stools 3/8 (37.5%) 3
Difficulty Swallowing Pills 1/8 (12.5%) 1
Dyspepsia 1/8 (12.5%) 1
Bloating 1/8 (12.5%) 1
Cramping in neck 1/8 (12.5%) 1
General disorders
Fatigue 2/8 (25%) 2
Insomnia 1/8 (12.5%) 1
Night sweats 1/8 (12.5%) 1
Weight Gain 1/8 (12.5%) 1
Belching 1/8 (12.5%) 1
Skin Redness 1/8 (12.5%) 1
Ankle Tenderness/Pain 2/8 (25%) 2
Back Pain 2/8 (25%) 2
Chest Pain 1/8 (12.5%) 1
Metabolism and nutrition disorders
Increased ALT 2/8 (25%) 2
Increased AST 3/8 (37.5%) 3
Hypoalbuminemia 1/8 (12.5%) 1
Hyperglycemia 8/8 (100%) 8
Hyperuricemia 4/8 (50%) 4
Increased Creatinine 1/8 (12.5%) 1
hypomagnesemia 2/8 (25%) 2
hypophosphatemia 1/8 (12.5%) 1
Nervous system disorders
Mood Changes 1/8 (12.5%) 1
Headache 2/8 (25%) 2
Respiratory, thoracic and mediastinal disorders
Dyspnea 2/8 (25%) 2
Upper Respiratory Infection 1/8 (12.5%) 1
Viral Respiratory Infection 1/8 (12.5%) 1
Sinus Congestion 1/8 (12.5%) 1
Post Nasal Drip 1/8 (12.5%) 1
Skin and subcutaneous tissue disorders
Palpable left axillary and mandibular lymph nodes 1/8 (12.5%) 1
Brusing left arm 1/8 (12.5%) 1
Shingles 1/8 (12.5%) 1
Jock Itch 1/8 (12.5%) 1

Limitations/Caveats

Low accrual and early termination limits the conclusions one could draw. Although no pts on this trial met the primary endpoint of a 25% or greater M-protein reduction, the small number of pts enrolled prohibits formal statistical analysis.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Jeffrey Zonder, M.D.
Organization Barbara Ann Karmanos Cancer Institute
Phone 313-576-8732
Email zonderj@karmanos.org
Responsible Party:
Jeffrey Zonder, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00942422
Other Study ID Numbers:
  • CDR0000646899
  • P30CA022453
  • WSU-2009-015
  • NCT01589887
First Posted:
Jul 20, 2009
Last Update Posted:
Mar 27, 2015
Last Verified:
Mar 1, 2015