Immunoglobulin for Hypogammaglobulinemia Due to Chimeric Antigen Receptor T Cell Therapy

Recruiting

• Conditions: Hypogammaglobulinemia, Acquired
• Interventions: Biological: Immune Globulin Intravenous (Human), 10%; Biological: Immune Globulin Subcutaneous (Human), 20% Solution

• Registration Number: NCT06989541
• Lead Sponsor: University of Alberta

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.

Study Timeline

• Study First Submitted: 2025-05-16
• Study First Submitted QC: 2025-05-16
• Study First Posted: 2025-05-25
• Study Start: 2025-06-01
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-02
• Last Update Posted: 2025-07-03
• Primary Completion: 2027-05-01
• Study Completion: 2027-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
IVIG	Immune Globulin Intravenous (Human), 10%	Intravenous Immunoglobulin Replacement
SCIG	Immune Globulin Subcutaneous (Human), 20% Solution	Subcutaneous Immunoglobulin Replacement

Primary Outcome Measures

Name	Time	Method
Time normalized rate of infections grade 3 or greater	40 weeks	Time normalized rate of infections grade 3 or greater

Secondary Outcome Measures

Name	Time	Method
Days on therapeutic antibiotics	40 weeks	Days on therapeutic antibiotics for treatment of an infection (excluding days on routinely provided prophylactic antibiotics)
Total number of days of hospitalizations due to infections	40 weeks	Total number of days of hospitalizations due to infections (rate per subject-year)
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)
IRT-related adverse events	40 weeks	Nature and frequency of immune globulin-related adverse events
Mean leukocyte counts at the last study visit	40 weeks	Mean leukocyte counts at the 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
Geometric mean of IgG serum trough concentration	40 weeks	Geometric mean of IgG serum trough concentration at last study visit
Mean total grams of immunoglobulin administered	40 weeks	Mean total grams of immunoglobulin administered per patient-year
Mean TSQM9	40 weeks	Treatment Satisfaction Questionnaire for Medication (TSQM9)
Hours of infusion clinic time required for IVIG administration	40 weeks	Hours of infusion clinic time required for IVIG administration

Trial Locations

Locations (1)

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada