Trial Outcomes & Findings for Green Tea Extract in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia (NCT NCT00262743)

NCT ID: NCT00262743

Last Updated: 2013-05-30

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

73 participants

Primary outcome timeframe

6 months

Results posted on

2013-05-30

Participant Flow

A total of 73 participants were enrolled at the Mayo Clinic from August 2005 - October 2009.

Thirty-six (36) and 37 patients recruited to the phase I and phase II portions, respectively. Three phase I patients were replaced and one patient was ineligible for evaluation. Per study design, the 36 eligible phase II participants along with the 6 phase I participants treated at the phase II dose level were evaluated (n=42).

Participant milestones

Participant milestones
Measure
Phase I Polyphenon E
Dose ranging from 400 to 1,800 mg orally twice a day for 6 months
Phase II Polyphenon E
2000mg orally twice daily for 6 months
Overall Study
STARTED
27
42
Overall Study
COMPLETED
27
30
Overall Study
NOT COMPLETED
0
12

Reasons for withdrawal

Reasons for withdrawal
Measure
Phase I Polyphenon E
Dose ranging from 400 to 1,800 mg orally twice a day for 6 months
Phase II Polyphenon E
2000mg orally twice daily for 6 months
Overall Study
Adverse Event
0
9
Overall Study
Disease progression
0
3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Phase I Polyphenon E
n=27 Participants
Dose ranging from 400 to 1,800 mg orally twice daily for 6 months
Phase II Polyphenon E
n=42 Participants
2000mg twice daily for 6 months
Total
n=69 Participants
Total of all reporting groups
Age Continuous
62 years
n=5 Participants
60 years
n=7 Participants
60 years
n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
12 Participants
n=7 Participants
21 Participants
n=5 Participants
Sex: Female, Male
Male
18 Participants
n=5 Participants
30 Participants
n=7 Participants
48 Participants
n=5 Participants
Region of Enrollment
United States
27 participants
n=5 Participants
42 participants
n=7 Participants
69 participants
n=5 Participants
Dose Level of Polyphenon E
400 mg
3 participants
n=5 Participants
0 participants
n=7 Participants
3 participants
n=5 Participants
Dose Level of Polyphenon E
800 mg
6 participants
n=5 Participants
0 participants
n=7 Participants
6 participants
n=5 Participants
Dose Level of Polyphenon E
1000 mg
3 participants
n=5 Participants
0 participants
n=7 Participants
3 participants
n=5 Participants
Dose Level of Polyphenon E
1200 mg
6 participants
n=5 Participants
0 participants
n=7 Participants
6 participants
n=5 Participants
Dose Level of Polyphenon E
1400 mg
3 participants
n=5 Participants
0 participants
n=7 Participants
3 participants
n=5 Participants
Dose Level of Polyphenon E
1600 mg
3 participants
n=5 Participants
0 participants
n=7 Participants
3 participants
n=5 Participants
Dose Level of Polyphenon E
1800 mg
3 participants
n=5 Participants
0 participants
n=7 Participants
3 participants
n=5 Participants
Dose Level of Polyphenon E
2000 mg
0 participants
n=5 Participants
42 participants
n=7 Participants
42 participants
n=5 Participants
Fluorescence In Situ Hybridization (FISH) Abnormalities
Normal
6 participants
n=5 Participants
10 participants
n=7 Participants
16 participants
n=5 Participants
Fluorescence In Situ Hybridization (FISH) Abnormalities
deletion (13q14.2)
17 participants
n=5 Participants
27 participants
n=7 Participants
44 participants
n=5 Participants
Fluorescence In Situ Hybridization (FISH) Abnormalities
Trisomy 12
4 participants
n=5 Participants
4 participants
n=7 Participants
8 participants
n=5 Participants
Fluorescence In Situ Hybridization (FISH) Abnormalities
deletion (11q23)
0 participants
n=5 Participants
1 participants
n=7 Participants
1 participants
n=5 Participants
Rai Stage
Stage 0
15 participants
n=5 Participants
13 participants
n=7 Participants
28 participants
n=5 Participants
Rai Stage
Stage I
8 participants
n=5 Participants
24 participants
n=7 Participants
32 participants
n=5 Participants
Rai Stage
Stage II
4 participants
n=5 Participants
5 participants
n=7 Participants
9 participants
n=5 Participants
ZAP-70 Status
Positive (>=20%)
6 participants
n=5 Participants
12 participants
n=7 Participants
18 participants
n=5 Participants
ZAP-70 Status
Negative (<20%)
21 participants
n=5 Participants
30 participants
n=7 Participants
51 participants
n=5 Participants
CD38 Status
Positive (>=30%)
4 participants
n=5 Participants
7 participants
n=7 Participants
11 participants
n=5 Participants
CD38 Status
Negative (<30%)
23 participants
n=5 Participants
35 participants
n=7 Participants
58 participants
n=5 Participants
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status
Unmutated (<=2%)
7 participants
n=5 Participants
6 participants
n=7 Participants
13 participants
n=5 Participants
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status
Mutated (>2%)
18 participants
n=5 Participants
27 participants
n=7 Participants
45 participants
n=5 Participants
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status
Unavailable
2 participants
n=5 Participants
9 participants
n=7 Participants
11 participants
n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Phase II participants who satisfied all eligibility criteria, signed the consent form and started therapy were evaluated for this endpoint.

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

Outcome measures

Outcome measures
Measure
Phase II Polyphenon E
n=42 Participants
2000mg twice daily for 6 months
Number of Participants With a Confirmed Response [Complete Response (CR) and Partial Response (PR)] on 2 Consecutive Evaluations at Least 4 Weeks Apart
1 participants

PRIMARY outcome

Timeframe: 6 months

Population: Phase II participants who satisfied all eligibility criteria, signed the consent form and started therapy were evaluated for this endpoint.

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

Outcome measures

Outcome measures
Measure
Phase II Polyphenon E
n=42 Participants
2000mg twice daily for 6 months
Number of Participants With Biological Response (Bio-R) on 2 Consecutive Evaluations at Least 4 Weeks Apart
28 participants

SECONDARY outcome

Timeframe: 6 months

Population: Phase II participants who satisfied all eligibility criteria, signed the consent form and started therapy were evaluated for this endpoint.

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.

Outcome measures

Outcome measures
Measure
Phase II Polyphenon E
n=42 Participants
2000mg twice daily for 6 months
Number of Participants With a Confirmed Complete Response (CR)
0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months (from registration)

Population: Phase II participants who satisfied all eligibility criteria, signed the consent form and started therapy were evaluated for this endpoint.

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.

Outcome measures

Outcome measures
Measure
Phase II Polyphenon E
n=42 Participants
2000mg twice daily for 6 months
24 Month Treatment Free Survival Rate
79 percentage of participants
Interval 62.0 to 92.0

Adverse Events

Phase II Polyphenon E

Serious events: 0 serious events
Other events: 40 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Phase II Polyphenon E
n=42 participants at risk
2000mg orally twice daily for 6 months
Blood and lymphatic system disorders
Hemoglobin decreased
28.6%
12/42 • Number of events 27
Eye disorders
Vision blurred
2.4%
1/42 • Number of events 1
Gastrointestinal disorders
Abdominal distension
28.6%
12/42 • Number of events 21
Gastrointestinal disorders
Abdominal pain
47.6%
20/42 • Number of events 37
Gastrointestinal disorders
Constipation
11.9%
5/42 • Number of events 5
Gastrointestinal disorders
Diarrhea
69.0%
29/42 • Number of events 68
Gastrointestinal disorders
Dyspepsia
28.6%
12/42 • Number of events 24
Gastrointestinal disorders
Esophageal ulcer
2.4%
1/42 • Number of events 1
Gastrointestinal disorders
Flatulence
35.7%
15/42 • Number of events 32
Gastrointestinal disorders
Mucositis oral
9.5%
4/42 • Number of events 4
Gastrointestinal disorders
Nausea
64.3%
27/42 • Number of events 71
Gastrointestinal disorders
Vomiting
11.9%
5/42 • Number of events 5
General disorders
Edema limbs
2.4%
1/42 • Number of events 1
General disorders
Fatigue
52.4%
22/42 • Number of events 59
General disorders
Fever
2.4%
1/42 • Number of events 1
General disorders
Flu-like symptoms
23.8%
10/42 • Number of events 12
Immune system disorders
Hypersensitivity
2.4%
1/42 • Number of events 1
Infections and infestations
Infection
2.4%
1/42 • Number of events 1
Infections and infestations
Skin infection
2.4%
1/42 • Number of events 1
Infections and infestations
Upper respiratory infection
2.4%
1/42 • Number of events 1
Infections and infestations
Urinary tract infection
2.4%
1/42 • Number of events 2
Investigations
Alanine aminotransferase increased
52.4%
22/42 • Number of events 57
Investigations
Alkaline phosphatase increased
14.3%
6/42 • Number of events 30
Investigations
Aspartate aminotransferase increased
45.2%
19/42 • Number of events 32
Investigations
Blood bilirubin increased
9.5%
4/42 • Number of events 13
Investigations
Creatinine increased
2.4%
1/42 • Number of events 2
Investigations
Neutrophil count decreased
11.9%
5/42 • Number of events 11
Investigations
Platelet count decreased
35.7%
15/42 • Number of events 34
Metabolism and nutrition disorders
Anorexia
33.3%
14/42 • Number of events 25
Metabolism and nutrition disorders
Blood glucose increased
16.7%
7/42 • Number of events 18
Metabolism and nutrition disorders
Dehydration
2.4%
1/42 • Number of events 1
Metabolism and nutrition disorders
Glucose intolerance
2.4%
1/42 • Number of events 1
Metabolism and nutrition disorders
Serum calcium decreased
7.1%
3/42 • Number of events 8
Metabolism and nutrition disorders
Serum calcium increased
2.4%
1/42 • Number of events 1
Metabolism and nutrition disorders
Serum potassium increased
4.8%
2/42 • Number of events 2
Metabolism and nutrition disorders
Serum sodium decreased
2.4%
1/42 • Number of events 1
Musculoskeletal and connective tissue disorders
Arthralgia
2.4%
1/42 • Number of events 2
Musculoskeletal and connective tissue disorders
Back pain
4.8%
2/42 • Number of events 5
Musculoskeletal and connective tissue disorders
Bone pain
2.4%
1/42 • Number of events 1
Musculoskeletal and connective tissue disorders
Buttock pain
2.4%
1/42 • Number of events 1
Musculoskeletal and connective tissue disorders
Myalgia
2.4%
1/42 • Number of events 5
Nervous system disorders
Dizziness
11.9%
5/42 • Number of events 6
Nervous system disorders
Extrapyramidal disorder
2.4%
1/42 • Number of events 1
Nervous system disorders
Headache
31.0%
13/42 • Number of events 21
Nervous system disorders
Peripheral sensory neuropathy
2.4%
1/42 • Number of events 1
Psychiatric disorders
Insomnia
4.8%
2/42 • Number of events 2
Skin and subcutaneous tissue disorders
Alopecia
4.8%
2/42 • Number of events 2
Skin and subcutaneous tissue disorders
Pruritus
2.4%
1/42 • Number of events 1
Skin and subcutaneous tissue disorders
Rash desquamating
7.1%
3/42 • Number of events 6
Skin and subcutaneous tissue disorders
Sweating
4.8%
2/42 • Number of events 2

Additional Information

Dr. Tait Shanafelt

Mayo Clinic

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place