Humoral Immunodeficiency in CLL and Therapy With Subcutaneous Ig

Study Overview
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Brief Summary
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Patients with chronic lymphocytic leukemia (CLL) are at increased risk of infections as compared to age matched controls, with infections being a major cause of morbidity and mortality. Previous studies have shown that patients with CLL have both hypogammaglobinemia and impaired humoral immunity as defined by vaccine responses to both polysaccharide and peptide antigens. Attempts at decreasing infections in CLL have included therapy with prophylactic antibiotics and intravenous immunoglobulin. In general clinical practice and in previous studies, patients have started IV immunoglobulin replacement therapy if they have a history of serious infection or hypogammaglobinemia (defined as Immunoglobulin G below 500-600 g/dL), but vaccine responses have not been evaluated. This study will identify CLL patients with humoral immunodeficiency by checking both Ig levels and vaccines responses. In patients with impaired humoral immunity, the investigators will use subcutaneous immunoglobulin replacement to show this intervention will increase Ig levels, protective antibody titers, and be well tolerated.

Official Title
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A Prospective Case Series of Subcutaneous Immunoglobulin for Prophylaxis of Infections in Patients With Chronic Lymphocytic Leukemia With Impaired Humoral Immunity

Conditions
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Secondary Immune Deficiency Disorder

Intervention / Treatment
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* Drug: Hizentra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic lymphocytic leukemia Medically stable, with expected survival of > 1 year Able to understand and willingness to sign a written informed consent Able to comply with study procedures Exclusion Criteria: Previously diagnosed primary immunodeficiency Additional immunosuppressive states as assessed by the primary or co investigators Ongoing therapy with Ig replacement Serum IgG < 500 mg/dL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ig replacement<br>Subjects will receive Hizentra 0.4 mg/kg subq once weekly. | Drug: Hizentra<br>* Subjects will receive Hizentra 0.4 mg/kg qweekly subcutaneously for 6 months (24 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify patients with CLL with humoral immunodeficiency despite serum IgG > 500 mg/dL. | Incidence of humoral immunodeficiency | 10 months | 
| Number of patients who increase IgG to above 700 mg/dL | Effectiveness of Hizentra to change IgG levels | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who increase diphtheria IgG to above 0.1 IU/mL, tetanus IgG to above 0.1 IU/mL, and IgG to streptococcus pneumonia to above 1.3 mcg/mL | Effectiveness of Hizentra to change specific antibody titers in CLL | 10 months | 
| Number of subjects with treatment-related adverse effects as assessed by CTCAE v4.0 | Safety and tolerability of Hizentra in CLL | 10 months | 
| Quality of life (Short Form 36) on subcutaneous Ig replacement therapy a 0-100 scale, with lower scores indicating higher disability/lower quality of life | Does Hizentra change quality of life scores in patients with CLL | 10 months | 
| Track the number of infections requiring antibiotics, further characterized per severity as defined in previous studies | Does Hizentra change the rate of non-neutropenic infections in CLL | 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic lymphocytic leukemia