Imprime PGG, Alemtuzumab, and Rituximab in Treating Patients With High Risk Chronic Lymphocytic Leukemia
|ClinicalTrials.gov Identifier: NCT01269385|
Recruitment Status : Unknown
Verified June 2015 by Mayo Clinic.
Recruitment status was: Active, not recruiting
First Posted : January 4, 2011
Last Update Posted : April 21, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|B-cell Chronic Lymphocytic Leukemia Refractory Chronic Lymphocytic Leukemia Stage 0 Chronic Lymphocytic Leukemia Stage I Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia||Biological: alemtuzumab Biological: rituximab Drug: PGG beta-glucan Other: flow cytometry Other: laboratory biomarker analysis Genetic: DNA analysis Genetic: fluorescence in situ hybridization Genetic: polymerase chain reaction Genetic: polymorphism analysis Genetic: mutation analysis||Phase 1 Phase 2|
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 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Early Treatment of High Risk Chronic Lymphocytic Leukemia With Alemtuzumab, Rituximab, and PGG Beta-Glucan: A Phase I/II Trial|
|Study Start Date :||January 2011|
|Actual Primary Completion Date :||June 2014|
Experimental: Arm I
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.
Other Names:Biological: rituximab
Other Names:Drug: PGG beta-glucan
Other Name: Imprime PGGOther: flow cytometry
Correlative studiesOther: laboratory biomarker analysis
Correlative studiesGenetic: DNA analysis
Correlative studiesGenetic: fluorescence in situ hybridization
Other Name: fluorescence in situ hybridization (FISH)Genetic: polymerase chain reaction
Other Name: PCRGenetic: polymorphism analysis
Correlative studiesGenetic: mutation analysis
- To determine the maximum tolerated dose (MTD) of PGG beta glucan in combination with alemtuzumab and rituximab (Phase I) [ Time Frame: At least 5 weeks ]
- Proportion of complete responses (Phase II) [ Time Frame: 3 months after the completion of treatment ]
- Overall response rate as estimated by the total number of complete responses or partial responses (CR or PR) divided by the total number of evaluable patients (Phase II) [ Time Frame: 3 months after the completion of treatment ]
- Time to disease progression (Phase II) [ Time Frame: Up to 5 years ]
- Duration of response for all evaluable patients who have achieved an objective response (Phase II) [ Time Frame: Up to 5 years ]
- Time to subsequent therapy (Phase II) [ Time Frame: Up to 5 years ]
- The number and severity of all adverse events (Phase I) [ Time Frame: At least 5 weeks ]
- Toxicity profile, including non-hematologic toxicities; hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia; and overall toxicity incidence as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 (Phase I) [ Time Frame: At least 5 weeks ]
- The number and severity of grade 3+ adverse events (Phase I) [ Time Frame: At least 5 weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01269385
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Steven Ansell, M.D.||Mayo Clinic|