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

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT01269385
Collaborator
National Cancer Institute (NCI) (NIH)
22
1
1
53
0.4

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • 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

Detailed Description

PRIMARY OBJECTIVES:
  1. 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
SECONDARY OBJECTIVES:
  1. 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).

  2. To assess the rate of overall response in CLL patients using this treatment regimen.

  3. To determine time to progression, time to next treatment, and duration of response in CLL patients using this treatment regimen.

TERTIARY OBJECTIVES:
  1. To assess the correlation between the individual prognostic markers (17p-, 11q-, unmutated VH gene, use of VH3-21, ZAP70+, CD38+) and clinical outcome.

  2. 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 Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 :
Jan 1, 2011
Actual Primary Completion Date :
Jun 1, 2014
Actual Study Completion Date :
Jun 1, 2015

Arms and Interventions

Arm Intervention/Treatment
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.

Biological: alemtuzumab
Given subcutaneously
Other Names:
  • anti-CD52 monoclonal antibody
  • Campath-1H
  • MoAb CD52
  • Monoclonal Antibody Campath-1H
  • Monoclonal Antibody CD52
  • Biological: rituximab
    Given IV
    Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
  • Drug: PGG beta-glucan
    Given IV
    Other Names:
  • Imprime PGG
  • Other: flow cytometry
    Correlative studies

    Other: laboratory biomarker analysis
    Correlative studies

    Genetic: DNA analysis
    Correlative studies

    Genetic: fluorescence in situ hybridization
    Correlative studies
    Other Names:
  • fluorescence in situ hybridization (FISH)
  • Genetic: polymerase chain reaction
    Correlative studies
    Other Names:
  • PCR
  • Genetic: polymorphism analysis
    Correlative studies

    Genetic: mutation analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. 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) [First cycle of treatment (35 days)]

      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.

    2. Proportion of Complete Responses (Dose Level 2) [3 months after the completion of treatment, up to 5 years]

      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.

    Secondary Outcome Measures

    1. Overall Response Rate (Dose Level 2) [3 months after the completion of treatment, up to 5 years]

      Overall response rate was estimated by the total number of patients receiving Dose Level 2 reporting complete responses or partial responses (CR or PR) divided by the total number of evaluable patients that started Dose Level 2 treatment. A COMPLETE RESPONSE (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. A PARTIAL RESPONSE (PR) requires the patient exhibits at least two of the features: ≥ 50% decrease in peripheral blood lymphocyte count from baseline, ≥ 50% reduction in the sum of the products of the maximal perpendicular diameters of the largest measured node or nodal masses in the right and left cervical, axillary, and inguinal lymph node regions on physical examination.

    2. Time to Disease Progression [Up to 5 years]

      Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier.

    3. Duration of Response for All Evaluable Patients Who Have Achieved an Objective Response [Up to 5 years]

      Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.

    4. Time to Subsequent Therapy [Up to 5 years]

      Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier.

    5. Number of Participants With Grade 3+ Adverse Events [up to 5 years of treatment]

      Adverse events were collected at the end of each cycle according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of grade 3+ events at least possibly related to treatment are recorded. For a complete set of all recorded adverse events, please see the Adverse Events section of this report.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Steven Ansell, M.D., Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT01269385
    Other Study ID Numbers:
    • LS1084
    • NCI-2010-02329
    • LS1084
    • 10-003025
    First Posted:
    Jan 4, 2011
    Last Update Posted:
    Jun 23, 2020
    Last Verified:
    Aug 1, 2018

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Phase I: Dose Level 0 Phase I: Dose Level 1 Phase I: Dose Level 2 Phase II: Dose Level 2
    Arm/Group Description During one 35-day period of treatment: Patients receive 1 mg/kg/dose PGG (poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose) IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity. During one 35-day period of treatment: Patients receive 2 mg/kg/dose PGG (poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose) IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity. During one 35-day period of treatment: Patients receive 4 mg/kg/dose PGG (poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose) IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity. During one 35-day period of treatment: Patients receive 4 mg/kg/dose PGG (poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose) IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED 4 4 6 8
    COMPLETED 3 3 6 8
    NOT COMPLETED 1 1 0 0

    Baseline Characteristics

    Arm/Group Title All Patients
    Arm/Group Description During one 35-day period of treatment: Patients receive 1, 2, or 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Overall Participants 20
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    61
    Sex: Female, Male (Count of Participants)
    Female
    6
    30%
    Male
    14
    70%
    Region of Enrollment (participants) [Number]
    United States
    20
    100%

    Outcome Measures

    1. Primary Outcome
    Title 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)
    Description 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.
    Time Frame First cycle of treatment (35 days)

    Outcome Measure Data

    Analysis Population Description
    All Phase I patients that were eligible and completed cycle 1 treatment were used in the MTD assessment.
    Arm/Group Title Phase I: Dose Level 0 Phase I: Dose Level 1 Phase I: Dose Level 2
    Arm/Group Description During one 35-day period of treatment: Patients receive 1 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity. During one 35-day period of treatment: Patients receive 2 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity. During one 35-day period of treatment: Patients receive 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Measure Participants 3 3 6
    Count of Participants [Participants]
    0
    0%
    0
    NaN
    1
    NaN
    2. Primary Outcome
    Title Proportion of Complete Responses (Dose Level 2)
    Description 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.
    Time Frame 3 months after the completion of treatment, up to 5 years

    Outcome Measure Data

    Analysis Population Description
    All patients treated at dose level 2 were included in this analysis. This includes 6 patients registered to the Phase I: Dose level 2 and 8 patients registered to Phase II.
    Arm/Group Title Dose Level 2
    Arm/Group Description During one 35-day period of treatment: Patients receive 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Measure Participants 14
    Number (95% Confidence Interval) [proportion of participants]
    .65
    3.3%
    3. Secondary Outcome
    Title Overall Response Rate (Dose Level 2)
    Description Overall response rate was estimated by the total number of patients receiving Dose Level 2 reporting complete responses or partial responses (CR or PR) divided by the total number of evaluable patients that started Dose Level 2 treatment. A COMPLETE RESPONSE (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. A PARTIAL RESPONSE (PR) requires the patient exhibits at least two of the features: ≥ 50% decrease in peripheral blood lymphocyte count from baseline, ≥ 50% reduction in the sum of the products of the maximal perpendicular diameters of the largest measured node or nodal masses in the right and left cervical, axillary, and inguinal lymph node regions on physical examination.
    Time Frame 3 months after the completion of treatment, up to 5 years

    Outcome Measure Data

    Analysis Population Description
    All patients treated at dose level 2 were included in this analysis. This includes 6 patients registered to the Phase I: Dose level 2 and 8 patients registered to Phase II.
    Arm/Group Title Dose Level 2
    Arm/Group Description During one 35-day period of treatment: Patients receive 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Measure Participants 14
    Number (95% Confidence Interval) [proportion of patients]
    .93
    4. Secondary Outcome
    Title Time to Disease Progression
    Description Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    All 20 eligible patients that started and completed protocol treatment were combined in this analysis to assess overall benefit of protocol treatment.
    Arm/Group Title All Patients
    Arm/Group Description During one 35-day period of treatment: Patients receive 1, 2, or 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Measure Participants 20
    Median (95% Confidence Interval) [months]
    17.6
    5. Secondary Outcome
    Title Duration of Response for All Evaluable Patients Who Have Achieved an Objective Response
    Description Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Data was not collected to run this analysis.
    Arm/Group Title All Patients
    Arm/Group Description During one 35-day period of treatment: Patients receive 1, 2, or 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Measure Participants 0
    6. Secondary Outcome
    Title Time to Subsequent Therapy
    Description Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    All 20 eligible patients that started and completed protocol treatment were combined in this analysis to assess overall benefit of protocol treatment.
    Arm/Group Title All Patients
    Arm/Group Description During one 35-day period of treatment: Patients receive 1, 2, or 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Measure Participants 20
    Median (95% Confidence Interval) [months]
    NA
    7. Secondary Outcome
    Title Number of Participants With Grade 3+ Adverse Events
    Description Adverse events were collected at the end of each cycle according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of grade 3+ events at least possibly related to treatment are recorded. For a complete set of all recorded adverse events, please see the Adverse Events section of this report.
    Time Frame up to 5 years of treatment

    Outcome Measure Data

    Analysis Population Description
    All 20 eligible patients that started and completed protocol treatment were combined in this analysis to assess overall effect of protocol treatment.
    Arm/Group Title All Patients
    Arm/Group Description During one 35-day period of treatment: Patients receive 1, 2, or 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Measure Participants 20
    Grade 3 Adverse Event
    1
    5%
    Grade 4 Adverse Event
    2
    10%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Dose Level 0 Dose Level 1 Dose Level 2
    Arm/Group Description During one 35-day period of treatment: Patients receive 1 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3, 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity. During one 35-day period of treatment: Patients receive 2 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3, 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity. During one 35-day period of treatment: Patients receive 4 mg/kg/dose PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31 Alemtuzumab subcutaneously 3 mg day 3, 10 mg day 4 30 mg days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Rituximab 375 mg/m2 IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
    All Cause Mortality
    Dose Level 0 Dose Level 1 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/4 (0%) 0/14 (0%)
    Serious Adverse Events
    Dose Level 0 Dose Level 1 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 1/4 (25%) 4/14 (28.6%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Gastrointestinal disorders
    Diarrhea 0/4 (0%) 0 0/4 (0%) 0 2/14 (14.3%) 2
    Gastritis 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    General disorders
    Fever 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Metabolism and nutrition disorders
    Dehydration 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Skin and subcutaneous tissue disorders
    Urticaria 0/4 (0%) 0 1/4 (25%) 1 0/14 (0%) 0
    Vascular disorders
    Hypertension 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Hypotension 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Other (Not Including Serious) Adverse Events
    Dose Level 0 Dose Level 1 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 4/4 (100%) 14/14 (100%)
    Blood and lymphatic system disorders
    Anemia 4/4 (100%) 5 3/4 (75%) 6 11/14 (78.6%) 40
    Cardiac disorders
    Mitral valve disease 0/4 (0%) 0 1/4 (25%) 1 0/14 (0%) 0
    Gastrointestinal disorders
    Diarrhea 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Dyspepsia 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Nausea 0/4 (0%) 0 0/4 (0%) 0 2/14 (14.3%) 2
    Vomiting 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    General disorders
    Chills 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Fatigue 0/4 (0%) 0 0/4 (0%) 0 4/14 (28.6%) 6
    Fever 3/4 (75%) 5 2/4 (50%) 2 4/14 (28.6%) 5
    Immune system disorders
    Cytokine release syndrome 2/4 (50%) 2 1/4 (25%) 1 0/14 (0%) 0
    Infections and infestations
    Bladder infection 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Bronchial infection 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Infections and infestations - Other, specify 0/4 (0%) 0 0/4 (0%) 0 4/14 (28.6%) 5
    Lung infection 1/4 (25%) 1 1/4 (25%) 1 1/14 (7.1%) 2
    Peripheral nerve infection 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Pharyngitis 1/4 (25%) 1 0/4 (0%) 0 0/14 (0%) 0
    Sinusitis 0/4 (0%) 0 1/4 (25%) 1 0/14 (0%) 0
    Upper respiratory infection 1/4 (25%) 1 0/4 (0%) 0 3/14 (21.4%) 4
    Urinary tract infection 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Investigations
    Alanine aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Aspartate aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Lymphocyte count decreased 4/4 (100%) 7 4/4 (100%) 13 14/14 (100%) 43
    Lymphocyte count increased 1/4 (25%) 1 0/4 (0%) 0 0/14 (0%) 0
    Neutrophil count decreased 1/4 (25%) 1 1/4 (25%) 3 6/14 (42.9%) 7
    Platelet count decreased 3/4 (75%) 5 3/4 (75%) 9 7/14 (50%) 23
    White blood cell decreased 3/4 (75%) 3 2/4 (50%) 4 8/14 (57.1%) 15
    Metabolism and nutrition disorders
    Hyponatremia 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Hypophosphatemia 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Musculoskeletal and connective tissue disorders
    Arthritis 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 2
    Nervous system disorders
    Headache 0/4 (0%) 0 1/4 (25%) 1 0/14 (0%) 0
    Neuralgia 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Bronchospasm 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Skin and subcutaneous tissue disorders
    Erythema multiforme 1/4 (25%) 1 0/4 (0%) 0 0/14 (0%) 0
    Pruritus 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1
    Rash maculo-papular 2/4 (50%) 2 2/4 (50%) 3 9/14 (64.3%) 11
    Urticaria 0/4 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Stephen M. Ansell MD
    Organization Mayo Clinic
    Phone
    Email Ansell.Stephen@mayo.edu
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT01269385
    Other Study ID Numbers:
    • LS1084
    • NCI-2010-02329
    • LS1084
    • 10-003025
    First Posted:
    Jan 4, 2011
    Last Update Posted:
    Jun 23, 2020
    Last Verified:
    Aug 1, 2018