Contributions
Abstract: PB1504
Type: Publication Only
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Secondary immunodeficiency (SID) occurs as a consequence of hematological malignancies (HM), most commonly in chronic lymphocytic leukemia (CLL) and multiple myeloma. About 25% of patients present with SID at diagnosis of CLL and this incidence may increase to 85% during the course of disease. Recent advances in CLL therapy also lead to cumulative immunosuppression. Infections are the main cause of morbidity and mortality in CLL patients, causing between 30% and 50% of deaths within the first year after diagnosis. Intravenous immunoglobulin (IVIg) is established as secondary prophylaxis to reduce infection rates in patients with HM with hypogammaglobulinemia. No large randomized study has established efficacy of IVIg as primary prophylaxis in CLL patients with hypogammaglobulinemia yet, although several small studies suggest an up-to 4-fold reduction of infection rates.
Aims
The primary objective is to demonstrate the benefit of IVIg 10% compared to placebo as primary infection prophylaxis in patients with CLL and SID who undergo antineoplastic therapy.
Methods
This study is planned as a prospective, double-blind, randomized, placebo controlled, multicenter, interventional phase 3 study and will be conducted in approximately 50 centers in North America and Europe (EUDRA-CT #: 2019-004375-40). A minimum of 240 adults with a diagnosis of CLL will be enrolled and allocated 1:1 to either IVIg 10% (0.4 g/kg) plus standard of care (SoC) prophylaxis or placebo plus SoC prophylaxis. Patients will receive up to 13 infusions of IVIg in 4-weekly intervals. Total duration will be up to 55 weeks consisting of up to 3 weeks for screening, 48 weeks of treatment and 4 weeks of follow-up. Main inclusion criteria are CLL diagnosis according to International Workshop on CLL (iwCLL) criteria, undergoing CLL antineoplastic treatment, and hypogammaglobulinemia with IgG levels <500 mg/dL (5 g/L). Main exclusion criteria are IgG treatment within the last 3 months, antibiotic prophylaxis and/or treatment within 7 days prior to current CLL treatment start, as well as current major infection or ˃1 major infection in the previous 6 months before baseline. The primary efficacy outcome will be the occurrence of at least one major infection defined as (•) bacterial or viral infection resulting in death, (•) microbiologically or clinically documented bacterial or viral infection requiring treatment with anti-infectives, or (•) fever of unknown origin requiring hospitalization or hospitalization prolongation. Secondary outcomes include overall infection rate, frequency of SoC prophylaxis with anti-infectives, duration of anti-infective prophylaxis. Exploratory outcomes include quality of life measured by EQ-5D, IVIg PK profiles, and resource utilization. The primary efficacy evaluation is based on the comparison of major infections in CLL patients with or without primary infection prophylaxis with IVIg. The difference between these proportions will be statistically tested in the intent-to-treat (ITT) population. The Z approximation will be used for statistical comparison of the proportions observed. One-sided 97.5% confidence interval will be provided.
Results
Interim analysis will be conducted once at least 100 patients are available for evaluation of the primary endpoint in the ITT population).
Conclusion
This study will evaluate the efficacy and safety of IVIg 10% as primary prophylaxis of infections inCLL patients with SID in a large clinical setting for the first time.
Keyword(s): Chronic lymphocytic leukemia, Immune deficiency, Infection, IVIg
Abstract: PB1504
Type: Publication Only
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Secondary immunodeficiency (SID) occurs as a consequence of hematological malignancies (HM), most commonly in chronic lymphocytic leukemia (CLL) and multiple myeloma. About 25% of patients present with SID at diagnosis of CLL and this incidence may increase to 85% during the course of disease. Recent advances in CLL therapy also lead to cumulative immunosuppression. Infections are the main cause of morbidity and mortality in CLL patients, causing between 30% and 50% of deaths within the first year after diagnosis. Intravenous immunoglobulin (IVIg) is established as secondary prophylaxis to reduce infection rates in patients with HM with hypogammaglobulinemia. No large randomized study has established efficacy of IVIg as primary prophylaxis in CLL patients with hypogammaglobulinemia yet, although several small studies suggest an up-to 4-fold reduction of infection rates.
Aims
The primary objective is to demonstrate the benefit of IVIg 10% compared to placebo as primary infection prophylaxis in patients with CLL and SID who undergo antineoplastic therapy.
Methods
This study is planned as a prospective, double-blind, randomized, placebo controlled, multicenter, interventional phase 3 study and will be conducted in approximately 50 centers in North America and Europe (EUDRA-CT #: 2019-004375-40). A minimum of 240 adults with a diagnosis of CLL will be enrolled and allocated 1:1 to either IVIg 10% (0.4 g/kg) plus standard of care (SoC) prophylaxis or placebo plus SoC prophylaxis. Patients will receive up to 13 infusions of IVIg in 4-weekly intervals. Total duration will be up to 55 weeks consisting of up to 3 weeks for screening, 48 weeks of treatment and 4 weeks of follow-up. Main inclusion criteria are CLL diagnosis according to International Workshop on CLL (iwCLL) criteria, undergoing CLL antineoplastic treatment, and hypogammaglobulinemia with IgG levels <500 mg/dL (5 g/L). Main exclusion criteria are IgG treatment within the last 3 months, antibiotic prophylaxis and/or treatment within 7 days prior to current CLL treatment start, as well as current major infection or ˃1 major infection in the previous 6 months before baseline. The primary efficacy outcome will be the occurrence of at least one major infection defined as (•) bacterial or viral infection resulting in death, (•) microbiologically or clinically documented bacterial or viral infection requiring treatment with anti-infectives, or (•) fever of unknown origin requiring hospitalization or hospitalization prolongation. Secondary outcomes include overall infection rate, frequency of SoC prophylaxis with anti-infectives, duration of anti-infective prophylaxis. Exploratory outcomes include quality of life measured by EQ-5D, IVIg PK profiles, and resource utilization. The primary efficacy evaluation is based on the comparison of major infections in CLL patients with or without primary infection prophylaxis with IVIg. The difference between these proportions will be statistically tested in the intent-to-treat (ITT) population. The Z approximation will be used for statistical comparison of the proportions observed. One-sided 97.5% confidence interval will be provided.
Results
Interim analysis will be conducted once at least 100 patients are available for evaluation of the primary endpoint in the ITT population).
Conclusion
This study will evaluate the efficacy and safety of IVIg 10% as primary prophylaxis of infections inCLL patients with SID in a large clinical setting for the first time.
Keyword(s): Chronic lymphocytic leukemia, Immune deficiency, Infection, IVIg