Comparison of Immunoglobulin Replacement Therapy versus Antibiotic Prophylaxis for Infection Prevention in Adults with B-cell Acute Lymphoblastic Leukemia or B-cell Lymphoma Treated with CD19 CAR-T Cells

The primary objective is to compare immunoglobulin replacement therapy (IgRT) to antibiotic prophylaxis (AP) in preventing clinically or microbiologically documented infections within 12 months following randomization in patients treated with CD19-targeted Chimeric Antigen Receptor (CAR) T cells for B-cell acute lymphoblastic leukemia or B-cell lymphoma. The clinical endpoint is a composite outcome consisting of recurrent infections, defined as at least two episodes requiring curative systemic antibiotic treatment, or severe infections requiring hospitalization. 3

Secondary objectives include the evaluation of:

• Incidence of grade 3-4 severe infections;
• Rate of hospital readmission due to infections;
• Safety profiles of IgRT versus AP;
• Cost-effectiveness of both interventions;
• Immune reconstitution following CAR-T cell administration;
• Patient quality of life;
• Incidence of SARS-CoV-2 infection.

The sponsor did not provide information regarding the total number of participants. The study population consists of young adults and adults, aged 16 to 80 years, diagnosed with relapsed/refractory B-cell acute lymphoblastic leukemia or B-cell lymphoma. Eligible participants include those receiving CD19-targeted autologous CAR-T cell therapy and presenting with hypogammaglobulinemia, defined as immunoglobulin levels below 4g/L at the time of lymphodepletion. The cohort includes both male and female individuals. Patients with childbearing potential are required to utilize effective contraception for the duration of the study and for an additional 12 months following infusion.

This phase III, open-label, randomized clinical trial is designed to compare immunoglobulin replacement therapy (IgRT) with antibiotic prophylaxis (AP) to prevent clinically or microbiologically documented infections. The study focuses on patients aged 16 to 80 years diagnosed with B-cell acute lymphoblastic leukemia or B-cell lymphoma who are receiving CD19-targeted Chimeric Antigen Receptor (CAR)-T cells. Following randomization, participants will be monitored for a period of 12 months to assess a composite primary endpoint consisting of recurrent infections or severe infection. The research methodology includes assessments of immunoglobulin levels and lymphocyte counts at specific intervals, including months 1, 3, 6, 9, and 12. The end-of-study evaluation occurs at the 12-month mark. Participant involvement is expected to last for 12 months from the time of randomization, though the overall study recruitment and completion period is estimated between March 2026 and March 2029.

The investigational treatment consists of human normal immunoglobulin (IV), administered via the intravenous route at a dosage of 400 mg/kg.

The comparator treatments include the following antibiotic prophylaxis options:

• Amoxicillin trihydrate or amoxicillin sodium, administered at a dose of 1000 mg through the oral route.
• Sulfamethoxazole and trimethoprim, which includes bromhexine hydrochloride, administered at a dose of 800 mg via the oral route.
• Levofloxacin, administered at a dose of 500 mg through the oral route.
• Azithromycin, administered at a dose of 250 mg via the oral route.

The efficacy assessment in this study focuses on evaluating the prevention of clinically or microbiologically documented infections in patients with B-cell acute lymphoblastic leukemia or B-cell lymphoma following Chimeric Antigen Receptor (CAR)-T cell therapy. The primary endpoint is a composite outcome consisting of either recurrent infections, characterized by at least two episodes necessitating curative systemic antibiotic treatment, or a severe infection requiring hospitalization, measured from randomization to month 12.

Secondary efficacy parameters include:

• The cumulative hazard of severe infections requiring hospitalization within 12 months.
• The infection-free survival rate at month 12.
• The occurrence of COVID-19 infection within 12 months.
• The cumulative incidence of readmissions resulting from infectious episodes following hospital discharge after CAR-T cell infusion within 12 months.
• Lymphocyte counts, including IgA, IgG, IgM, CD19, CD4, and CD8, which are measured at lymphodepletion and at months 1, 3, 6, 9, and 12.
• Quality of life as assessed using the QLQ-C30 and EQ5D5L instruments.
• Cost effectiveness and cost utility evaluated through incremental cost effectiveness/utility ratios.