American Ginseng Extract in Preventing Respiratory Infection and in Reducing Antibiotic Use in Patients With CLL

• Number of ARI days during a fixed 3-month period [ Designated as safety issue: No ]
• Safety according to NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

• Number of antibiotic use days [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Rate of all infections [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Duration and severity of each ARI episode [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Incidence of major infections [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Incidence of herpes zoster [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Chronic lymphocytic leukemia disease activity [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Incidence and type of ARI in untreated cohort [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Incidence of confirmed influenza and respiratory syncytial virus by a physician [ Time Frame: 3 months ] [ Designated as safety issue: No ]

• Number of antibiotic use days [ Designated as safety issue: No ]
• Rate of all infections [ Designated as safety issue: No ]
• Duration and severity of each acute respiratory infection (ARI) episode [ Designated as safety issue: No ]
• Incidence of major infections [ Designated as safety issue: No ]
• Incidence of herpes zoster [ Designated as safety issue: No ]
• CLL disease activity [ Designated as safety issue: No ]
• Incidence and type of ARI in untreated cohort [ Designated as safety issue: No ]
• Incidence of confirmed influenza and RSV by a physician [ Designated as safety issue: No ]

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 phase III 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.

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.

• Dietary Supplement: American ginseng
  Given orally
• Dietary Supplement: placebo
  Given orally

• Experimental: Arm I
  Patients receive oral American ginseng extract twice daily.
  Intervention: Dietary Supplement: American ginseng
• Placebo Comparator: Arm II
  Patients receive oral placebo twice daily.
  Intervention: Dietary Supplement: placebo

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