Phase 2
Completed N=22
Imprime PGG, Alemtuzumab, and Rituximab in Treating Patients With High Risk Chronic Lymphocytic Leukemia
Source: ClinicalTrials.gov NCT01269385 ↗Enrolled (actual)
22
Serious AEs
22.7%
Results posted
Jun 2020
Primary outcomePrimary: Maximum Tolerated Dose (MTD) of PGG Beta Glucan in Combination With Alemtuzumab and Rituximab Assessed by Analyzing the Number of Dose-limiting Toxicity Events (Phase I) — 0; 0; 1 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of PGG Beta Glucan in Combination With Alemtuzumab and Rituximab Assessed by Analyzing the Number of Dose-limiting Toxicity Events (Phase I) |
0; 0; 1 | — |
| PRIMARY Proportion of Complete Responses (Dose Level 2) |
.65 | — |
| SECONDARY Overall Response Rate (Dose Level 2) |
.93 | — |
| SECONDARY Time to Disease Progression |
17.6 | — |
| SECONDARY Duration of Response for All Evaluable Patients Who Have Achieved an Objective Response |
— | — |
| SECONDARY Time to Subsequent Therapy |
NA | — |
| SECONDARY Number of Participants With Grade 3+ Adverse Events |
1; 2 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of CLL (Hallek, Cheson et al. 2008) manifested by: Minimum threshold peripheral lymphocyte count of 5 x 10^9/L AND immunophenotypic demonstrations of a population of B lymphocytes (as defined by CD19+) which are monoclonal (light chain exclusion); CLL will be diagnosed if these cells have >= 3 of the following characteristics: CD5+, CD23+, dim surface light chain expression, dim surface CD20 expression AND fluorescence in situ hybridization (FISH) analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression
- >= 1 of the following poor prognosis factors: unmutated IGHV ( = 30% cells positive on flow cytometry); unmutated IGHV ( = 20% cells positive on flow cytometry); use of VH3-21 gene segment irrespective of mutation status AND CD38 expression (>= 30% cells positive on flow cytometry); use of VH3-21 gene segment irrespective of mutation status AND ZAP-70 expression (>= 20% cells positive on flow cytometry); 11q22-; 17p13-
- Rai classification Stage 0, I or II that does not meet standard NCI-IWCLL criteria for treatment of CLL (Hallek, Cheson et al. 2008)
- Limited CLL disease burden with no lymph nodes > 5 cm in any diameter and splenomegaly < 6 cm below left costal margin in midclavicular line at rest
- Creatinine =< 1.5 x upper normal limit (UNL)
- Total bilirubin =< 3.0 x UNL; if total is elevated, a direct bilirubin should be performed and should be =< 1.5 x UNL
- AST =< 3.0 x UNL
- Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0, 1, or 2
- Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Provide informed written consent
- Willing to return to a Lymphoma Specialized Program of Research Excellence (SPORE) enrolling institution for follow-up
- Willing to provide blood samples for correlative research purposes
Exclusion Criteria
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- New York Heart Association Class III or IV heart disease
- Recent myocardial infarction (< 1 month)
- Uncontrolled infection
- Infection with the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), serological evidence of active hepatitis B infection (HBsAg or HBeAg positive) or positive hepatitis C serology, as further severe immunosuppression with this regimen may occur
- Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
- Other active primary malignancy requiring treatment or limits survival to =< 2 years
- Any major surgery =< 4 weeks prior to registration
- Any previous chemotherapy or monoclonal antibody treatment for CLL
- Current use of corticosteroids; NOTE: previous corticosteroids are allowed
Data sourced from ClinicalTrials.gov (NCT01269385). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.