Clinical trial NCT06989541: Immunoglobulin for Hypogammaglobulinemia Due to Chimeric Antigen Receptor T Cell Therapy
Official title: Immunoglobulin for Hypogammaglobulinemia Due to Chimeric Antigen Receptor T Cell Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypogammaglobulinemia, Acquired
Keywords: secondary immunodeficiency
CAR T
immune globulin
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2025-05-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated with CD19 targeted CAR T cell therapy for B cell malignancy

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time normalized rate of infections grade 3 or greater
timeFrame: 40 weeks
Secondary outcomes:
measure: Time normalized rate of validated infections
timeFrame: 40 weeks
measure: Days on therapeutic antibiotics
timeFrame: 40 weeks
measure: Days missed work/school/unable to perform normal daily activities due to infections
timeFrame: 40 weeks
measure: Total number of days of hospitalizations due to infections
timeFrame: 40 weeks
measure: Geometric mean of IgG serum trough concentration
timeFrame: 40 weeks
measure: Mean TSQM9
timeFrame: 40 weeks
measure: IRT-related adverse events
timeFrame: 40 weeks
measure: Hours of infusion clinic time required for IVIG administration
timeFrame: 40 weeks
measure: Mean total grams of immunoglobulin administered
timeFrame: 40 weeks
measure: Mean leukocyte counts at the last study visit
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
References: