Clinical trial NCT01269385
Conditions: B-cell Chronic Lymphocytic Leukemia Refractory Chronic Lymphocytic Leukemia Stage 0 Chronic Lymphocytic Leukemia Stage I Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia
Keywords: Imprime PGG
Sponsor: Mayo Clinic
Start date: 2011-01-01; Completion date: 2015-06-01
Enrollment: 22 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Monoclonal antibodies, such as alemtuzumab and rituximab, can kill chronic lymphocytic leukemia (CLL) cells and are effective therapies for this disease. Biological therapies, such as Imprime PGG (poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose), may stimulate the immune system in different ways and help monoclonal antibodies kill CLL cells. Giving PGG beta-glucan together with alemtuzumab and rituximab could make therapy with monoclonal antibodies, such as alemtuzumab and rituximab, more effective.

PURPOSE: This phase I/II trial is studying the side effects and best dose of PGG beta-glucan when given together with alemtuzumab and rituximab and to see how well it works in treating patients with earlier stage high-risk chronic lymphocytic leukemia.

Detailed description:
PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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 remission.

OUTLINE: This is phase I, dose-escalation study of PGG beta-glucan followed by a phase II study.

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.

Arms: arm 1: Patients receive PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31; alemtuzumab subcutaneously 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.
Interventions: intervention 1: alemtuzumab intervention 2: rituximab intervention 3: PGG beta-glucan intervention 4: flow cytometry intervention 5: laboratory biomarker analysis intervention 6: DNA analysis intervention 7: fluorescence in situ hybridization intervention 8: polymerase chain reaction intervention 9: polymorphism analysis intervention 10: mutation analysis
Intervention descriptions: intervention 1: Given subcutaneously intervention 2: Given IV intervention 3: Given IV intervention 4: Correlative studies intervention 5: Correlative studies intervention 6: Correlative studies intervention 7: Correlative studies intervention 8: Correlative studies intervention 9: Correlative studies intervention 10: Correlative studies

Protocol documents: