Imprime PGG, Alemtuzumab, and Rituximab in Treating Patients With High Risk Chronic Lymphocytic Leukemia

NCT ID: NCT01269385

Last Updated: 2020-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2015-06-30

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

alemtuzumab

Intervention Type: BIOLOGICAL

Given subcutaneously

rituximab

Intervention Type: BIOLOGICAL

Given IV

PGG beta-glucan

Intervention Type: DRUG

Given IV

flow cytometry

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

DNA analysis

Intervention Type: GENETIC

Correlative studies

fluorescence in situ hybridization

Intervention Type: GENETIC

Correlative studies

polymerase chain reaction

Intervention Type: GENETIC

Correlative studies

polymorphism analysis

Intervention Type: GENETIC

Correlative studies

mutation analysis

Intervention Type: GENETIC

Correlative studies

Interventions

alemtuzumab

Given subcutaneously

Intervention Type: BIOLOGICAL

rituximab

Given IV

Intervention Type: BIOLOGICAL

PGG beta-glucan

Given IV

Intervention Type: DRUG

flow cytometry

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

DNA analysis

Correlative studies

Intervention Type: GENETIC

fluorescence in situ hybridization

Correlative studies

Intervention Type: GENETIC

polymerase chain reaction

Correlative studies

Intervention Type: GENETIC

polymorphism analysis

Correlative studies

Intervention Type: GENETIC

mutation analysis

Correlative studies

Intervention Type: GENETIC

Other Intervention Names

anti-CD52 monoclonal antibody; Campath-1H; MoAb CD52; Monoclonal Antibody Campath-1H; Monoclonal Antibody CD52; IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; Imprime PGG; fluorescence in situ hybridization (FISH); PCR

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 (< 2%) AND CD38 expression (>= 30% cells positive on flow cytometry); unmutated IGHV (< 2%) AND ZAP-70 expression (>= 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Ansell, M.D.

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

NCI-2010-02329

Identifier Type: REGISTRY

Identifier Source: secondary_id

LS1084

Identifier Type: OTHER

Identifier Source: secondary_id

10-003025

Identifier Type: OTHER

Identifier Source: secondary_id

LS1084

Identifier Type: -

Identifier Source: org_study_id