Leukemia
Conditions
Keywords
stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
Brief summary
RATIONALE: American ginseng extract may prevent or reduce acute respiratory illness in patients with chronic lymphocytic leukemia. It is not yet known whether American ginseng extract is more effective than a placebo in preventing respiratory infections. PURPOSE: This randomized trial is studying the side effects of American ginseng extract and to see how well it works compared with a placebo in preventing respiratory infection and in reducing antibiotic use in patients with chronic lymphocytic leukemia.
Detailed description
OBJECTIVES: Primary * To assess the effect of American ginseng extract on the number of days of acute respiratory infection (ARI) during the peak respiratory illness season (January-March) in patients with chronic lymphocytic leukemia (CLL). * To determine the safety of American ginseng extract in these patients evaluated according to NCI CTCAE v3.0. Secondary * To assess the effect of this treatment on antibiotic use days (AUDs). * To assess the effect of this treatment on the rate of all infections diagnosed by a physician. * To assess the effect of this treatment on the duration and severity of each ARI episode. * To assess the effect of this treatment on major infections defined as infection severe enough to require hospitalization or intravenous antibiotics. * To assess the effect of this treatment on the incidence of herpes zoster infection defined as an episode of physician-diagnosed zoster infection. * To assess the effect of this treatment on CLL disease activity (i.e., serum IgG, total lymphocyte count, platelet count, and Rai staging). * To determine the incidence of ARI and type of illness in an untreated cohort of CLL patients over an entire winter respiratory illness season (January 1- April 30). Tertiary * To determine the effect of this treatment on the incidence of influenza and respiratory syncytial virus confirmed by a physician. OUTLINE: This is a multicenter study. Patients are stratified according to antibiotic prophylaxis with trimethoprim-sulfamethoxazole (yes vs no), serum IgG (≤ 500 mg/dL vs \> 500 mg/dL), and influenza vaccine status (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral American ginseng extract twice daily. * Arm II: Patients receive oral placebo twice daily. Treatment in both arms continues for up to 4 months in the absence of illness or adverse events. After completion of study treatment, patients are followed at 4 weeks by phone.
Interventions
DIETARY_SUPPLEMENTAmerican ginseng
Given orally
DIETARY_SUPPLEMENTPlacebo
Given orally
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of chronic lymphocytic leukemia (CLL) * Phenotypic evidence (i.e., flow cytometry or bone marrow biopsy) of disease * Untreated CLL allowed PATIENT CHARACTERISTICS: * ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% * Life expectancy \> 12 months * Creatinine \< 2.0 mg/dL OR creatinine clearance \> 50 mL/min * AST/ALT ≤ 2.5 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN * Not pregnant or nursing * Fertile patients must use effective contraception prior to and during study treatment * No known cirrhosis, collagen vascular disease, multiple sclerosis, or HIV positivity * No other prior or concurrent malignancies except for non-melanoma skin cancers or carcinoma in situ of the cervix * Other prior malignancies allowed provided the patient has been disease-free for \> 5 years * No uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * No psychiatric or social illness that would limit compliance with study requirements * No history of allergy or other adverse response to ginseng products * No history of seasonal or environmental allergies that require ongoing treatment with antihistamines, intranasal corticosteroids, or systemic corticosteroids PRIOR CONCURRENT THERAPY: * More than 3 months since prior and no concurrent chlorambucil * At least 1 month since prior and no other concurrent herbal ginseng products * No prior or concurrent fludarabine, alemtuzumab, rituximab, intravenous immunoglobulin, or hematopoietic stem cell transplantation * No concurrent corticosteroids (20 mg/day of prednisone or equivalent) * No concurrent antibiotic prophylaxis, except for trimethoprim-sulfamethoxazole * No concurrent warfarin * No other concurrent investigational or commercial agents or other therapies with the intent to treat the patient's malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Respiratory Infection (ARI) Days | 3 months | An ARI day was defined as any day for which the subject experienced one or more respiratory symptoms (cough, sore throat, nasal or sinus congestion, or runny nose) and one or more systemic symptoms (feverishness, chills/sweats, myalgia (muscle aches), fatigue, headache, poor endurance or increased shortness of breath) between January and March. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Antibiotic Use Days | 3 months | An antibiotic day was defined as a day on which the subject took one or more antibiotics between January and March. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I - Ginseng Patients receive oral American ginseng extract twice daily.
American ginseng: Given orally | 147 |
| Arm II - Placebo Patients receive oral placebo twice daily.
Placebo: Given orally | 146 |
| Total | 293 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 8 | 3 |
Baseline characteristics
| Characteristic | Arm I - Ginseng | Arm II - Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 76 Participants | 82 Participants | 158 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 64 Participants | 135 Participants |
| Age, Continuous | 65 years | 66 years | 65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 147 Participants | 144 Participants | 291 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 145 Participants | 141 Participants | 286 Participants |
| Region of Enrollment United States | 147 participants | 146 participants | 293 participants |
| Sex: Female, Male Female | 65 Participants | 60 Participants | 125 Participants |
| Sex: Female, Male Male | 82 Participants | 86 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 121 / 140 | 126 / 143 |
| serious Total, serious adverse events | 11 / 140 | 16 / 143 |
Outcome results
Primary
Acute Respiratory Infection (ARI) Days
An ARI day was defined as any day for which the subject experienced one or more respiratory symptoms (cough, sore throat, nasal or sinus congestion, or runny nose) and one or more systemic symptoms (feverishness, chills/sweats, myalgia (muscle aches), fatigue, headache, poor endurance or increased shortness of breath) between January and March.
Time frame: 3 months
Population: Participants who returned a respiratory symptom diary between January and March. Note that a few participants failed to provide respiratory diaries so the numbers of participants for these analyses do not necessarily match the numbers who remained in the study or the numbers with adverse event data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Ginseng | Acute Respiratory Infection (ARI) Days | 8.30 days | Standard Deviation 16.87 |
| Arm II - Placebo | Acute Respiratory Infection (ARI) Days | 6.78 days | Standard Deviation 13.27 |
p-value: 0.295Negative binomial regression
Secondary
Number of Antibiotic Use Days
An antibiotic day was defined as a day on which the subject took one or more antibiotics between January and March.
Time frame: 3 months
Population: Participants who returned respiratory symptom and antibiotic use diaries. Note that a few participants failed to provide antibiotic use diaries so the numbers of participants for these analyses do not necessarily match the numbers who remained in the study or the numbers with adverse event data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Ginseng | Number of Antibiotic Use Days | 1.12 days | Standard Deviation 3.42 |
| Arm II - Placebo | Number of Antibiotic Use Days | 1.55 days | Standard Deviation 6.46 |
p-value: 0.82Negative binomial regression