Early Treatment of High Risk Chronic Lymphocytic Leukemia With Alemtuzumab, Rituximab, and PGG Beta-Glucan: A Phase I/II Trial
I. Determine the maximum tolerated dose of PGG beta glucan in combination with alemtuzumab
and rituximab. (Phase I) II. Assess the rate of complete response of patients with
high-risk, early-intermediate stage CLL who are treated with alemtuzumab, rituximab, and PGG
beta glucan before meeting standard National Cancer Institute-International Workshop on
Chronic Lymphocytic Leukemia (NCI-IWCLL) criteria (Hallek, Cheson et al. 2008) for
treatment. (Phase II)
I. To monitor and assess toxicity of this regimen. II. Clinical evaluation of toxicity. III.
Serial monitoring of cytomegalovirus (CMV) viral load by polymerase chain reaction (PCR).
IV. To assess the rate of overall response in CLL patients using this treatment regimen.
V. To determine time to progression, time to next treatment, and duration of response in CLL
patients using this treatment regimen.
I. To assess the correlation between the individual prognostic markers (17p-, 11q-,
unmutated VH gene, use of VH3-21, ZAP70+, CD38+) and clinical outcome.
II. To assess response to this combination regimen using an expanded definition of response,
including bone marrow studies with immunohistochemical studies for residual CLL cells and
sensitive flow cytometry for minimal residual disease in patients in complete clinical
OUTLINE: This is phase I, dose-escalation study of PGG beta-glucan followed by a phase II
Patients receive PGG beta-glucan intravenously (IV) over 2-4 hours on days 1, 5, 10, 17, 24,
and 31; alemtuzumab subcutaneously (SC) on days 3, 4, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26,
29, 31, and 33; and rituximab IV on days 10, 17, 24, and 31. Treatment continues in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 3 months, every 3
months for 1 year, and then every 6 months for 5 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the maximum tolerated dose (MTD) of PGG beta glucan in combination with alemtuzumab and rituximab (Phase I)
At least 5 weeks
Clive Zent, M.D.
United States: Food and Drug Administration
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