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

NCT01269385 | Completed Phase 1 Results DMC

• 3 other identifiers: LS1084NCI-2010-0232910-003025
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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)

  MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. Three patients will be treated at a given dose level combination for at least 5 weeks to assess toxicity. If dose-limiting toxicity (DLT) is not seen in any of the 3 patients, 3 new patients will be accrued and treated at the next higher dose level. If DLT is seen in 2 or 3 of 3 patients treated at a given dose level, then the next 3 patients will be treated at the next lower dose level, if only 3 patients were enrolled and treated at this lower dose level. We tabulate the number of patients reporting a DLT.

  First cycle of treatment (35 days)

• Proportion of Complete Responses (Dose Level 2)

  The number of patients that demonstrate a Complete Response (CR) during treatment on Dose Level 2 divided by the number of eligible patients starting Dose Level 2 treatment. A CR requires all of the following for a period of at least 2 months: Absence of lymphadenopathy by physical examination, no hepatomegaly or splenomegaly, absence of constitutional symptoms, neutrophils \>1500/ul, Platelets \>100,000/ul, Hemoglobin \>11.0 gm/dl, Peripheral blood lymphocytes \<4000/uL.

  3 months after the completion of treatment, up to 5 years

Secondary Outcomes (5)

• Overall Response Rate (Dose Level 2)

  3 months after the completion of treatment, up to 5 years

• Time to Disease Progression

  Up to 5 years

• Duration of Response for All Evaluable Patients Who Have Achieved an Objective Response

  Up to 5 years

• Time to Subsequent Therapy

  Up to 5 years

• Number of Participants With Grade 3+ Adverse Events

  up to 5 years of treatment

Study Arms (1)

Arm I

EXPERIMENTAL

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.

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

Interventions

alemtuzumab BIOLOGICAL

Given subcutaneously

Also known as: anti-CD52 monoclonal antibody, Campath-1H, MoAb CD52, Monoclonal Antibody Campath-1H, Monoclonal Antibody CD52

Arm I

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Arm I

PGG beta-glucan DRUG

Given IV

Also known as: Imprime PGG

Arm I

flow cytometry OTHER

Correlative studies

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

DNA analysis GENETIC

Correlative studies

Arm I

fluorescence in situ hybridization GENETIC

Correlative studies

Also known as: fluorescence in situ hybridization (FISH)

Arm I

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Arm I

polymorphism analysis GENETIC

Correlative studies

Arm I

mutation analysis GENETIC

Correlative studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>= 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Alemtuzumab; Rituximab; Flow Cytometry; In Situ Hybridization, Fluorescence; Polymerase Chain Reaction; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization; Nucleic Acid Amplification Techniques; DNA Fingerprinting

Results Point of Contact

• Title: Stephen M. Ansell MD
• Organization: Mayo Clinic

Ansell.Stephen@mayo.edu

Study Officials

• Steven Ansell, M.D.

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: January 4, 2011
• Study Start: January 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2015
• Last Updated: June 23, 2020
• Results First Posted: June 23, 2020

Record last verified: 2018-08

Locations

US (1)