Hypogammaglobulinemia, Acquired
Conditions
Keywords
secondary immunodeficiency, CAR T, immune globulin
Brief summary
Chimeric antigen receptor (CAR) T cells are special immune cells taken from a patient and changed in a lab to help them find and attack cancer cells. These cells are designed to look for a marker called CD19, which is found on both cancer cells and healthy B cells (a type of white blood cell). Because of this, CAR T cells can also destroy healthy B cells. This can lead to a strong drop in B cells and cause a condition called hypogammaglobulinemia (HGG), which makes it harder for the body to fight infections. Serious infections are common in people treated with CAR T cells and are a major reason for death that is not caused by the return of cancer. To help prevent infections, patients with HGG often get immunoglobulin replacement therapy (IRT), which gives them the antibodies they need. This treatment can be given through a vein (IVIG) or under the skin (SCIG). The goal of this project is to study how often these patients get bacterial infections, how they feel about their quality of life and treatment, and what side effects they may have when treated with IVIG or SCIG after CAR T-cell therapy.
Detailed description
Chimeric antigen receptor (CAR) T cells are patient-derived T cells engineered to express a fusion protein that directs them to target a tumor-associated antigen. The tumor-associated antigen CD19 is expressed on tumor cells in these conditions as well as on healthy cells of the B cell lineage. This results the on-target off-tumor effect of profound B cell depletion in these patients often with attendant hypogammaglobulinemia (HGG). Serious infections are common in this patient population and represent the main cause of non-relapse related mortality in CAR T cell treated patients. Treatment of HGG with immunoglobulin replacement therapy (IRT) is a core component of infection prevention. Standard of care IRT can be administered intravenously (IVIG) or subcutaneously (SCIG). The proposed project will investigate frequency of bacterial infections, quality of life, treatment satisfaction, and adverse events in patients treated with CAR T-cell therapy who are treated with IVIG and SCIG.
Interventions
BIOLOGICALImmune Globulin Intravenous (Human), 10%
Intravenous immune globulin replacement
Subcutaneous immune globulin replacement
Sponsors
University of Alberta
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Severe HGG defined as total IgG \<4 g/L (after subtracting the IgG paraprotein fraction, if present) 3. Treated with CD19 targeted CAR T cell therapy in the past 6 months 4. Consent to receive plasma-derived productions 5. Ability to provide informed consent
Exclusion criteria
1. Inability to comply with study procedures 2. Pregnancy or planning to conceive 3. Breastfeeding 4. Protein-losing conditions that may contribute to HGG (e.g., protein-losing enteropathy, nephrotic syndrome) 5. SCIG infusion in the prior 3 months. 6. History of allergy or severe reactions to immune globulin productions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time normalized rate of infections grade 3 or greater | 40 weeks | Time normalized rate of infections grade 3 or greater |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days on therapeutic antibiotics | 40 weeks | Days on therapeutic antibiotics for treatment of an infection (excluding days on routinely provided prophylactic antibiotics) |
| Days missed work/school/unable to perform normal daily activities due to infections | 40 weeks | Days missed work/school/unable to perform normal daily activities due to infections (rate per subject-year) |
| Total number of days of hospitalizations due to infections | 40 weeks | Total number of days of hospitalizations due to infections (rate per subject-year) |
| Geometric mean of IgG serum trough concentration | 40 weeks | Geometric mean of IgG serum trough concentration at last study visit |
| Time normalized rate of validated infections | 40 weeks | Time normalized rate of infections (per subject-year) confirmed using microbiologic, clinical, and radiologic criteria |
| IRT-related adverse events | 40 weeks | Nature and frequency of immune globulin-related adverse events |
| Hours of infusion clinic time required for IVIG administration | 40 weeks | Hours of infusion clinic time required for IVIG administration |
| Mean total grams of immunoglobulin administered | 40 weeks | Mean total grams of immunoglobulin administered per patient-year |
| Mean leukocyte counts at the last study visit | 40 weeks | Mean leukocyte counts at the last study visit |
| Mean TSQM9 | 40 weeks | Treatment Satisfaction Questionnaire for Medication (TSQM9) |
Countries
Canada
Contacts
Primary ContactKathryn Rankin, PhD
Outcome results
None listed