Immunoglobulin Replacement Therapy (IgRT) Versus Antibiotic Prophylaxis (PA) in Patients Treated by CD19-targeted Chimeric Antigen Receptor (CAR)T Cells for a B Cell Acute Lymphoblastic Leukemia or a B Cell Lymphoma (PREV-CART)

A Multicentric Phase III Randomized Clinical Trial Open-label, Comparing Immunoglobulin Replacement Therapy (IgRT) and Antibiotic Prophylaxis (AP) in Patients Treated by CD19-targeted Chimeric Antigen Receptor (CAR)T Cells for a B Cell Acute Lymphoblastic Leukemia or a B Cell Lymphoma

B cell (CD19) targeted chimeric antigen receptor modified T Cells (CAR-T) has transformed treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) or B-cell lymphoma (BCL).

Because patients receiving CAR-T often present uncontrolled disease and have undergone several lines of treatment, they may be deeply immuno-depressed and prone to infections. Hypogammaglobulinemia were reported in 74% of patients preCAR-T cells infusion (Hill JA, et al. Blood Rev. 2019 Nov). CART cells also results in depletion of normal CD19+ B cells and hypogammaglobulinemia as an on-target, off tumor toxicity.

Because CAR-T cells can persist for years, patients are exposed to infectious complications secondary to long-term Bcell aplasia and severe hypogammaglobulinemia (<4g/l). Data from patients who received rituximab (CD20-specific monoclonal antibody) show that patients with severe hypogammaglobulinemia experienced recurrent bronchitis, sinusitis, pneumonia, and rarely, enteroviral meningoencephalitis. In patients receiving CAR T-cells, infection density is 0.55-0.67 infections/100 days3,5 at risk after the first month with a majority of respiratory and ENT (earsnose-throat) infections. To prevent infections, anti-bacterial prophylaxis (AP) based on local guidelines is often used in patients treated by CAR-T cells, with the risk of subsequent resistance. Otherwise, intravenous immunoglobulin replacement therapy (IgRT) is authorized by the French authorities for patients with secondary antibody deficiencies who developed severe or recurrent infections after appropriate antimicrobial therapy, if IgG levels <4g/l. However, although IgRT as primary prophylaxis (PP) have no approval, they are used as PP after CAR T-cells by many centers, with no data supporting such a strategy. The benefit of IgRT over AP as a primary prophylaxis in the setting of CD19 CAR-T cells therapy should be demonstrated given its burden for patients and care, as well as its cost and the risk of Ig shortage. Therefore, this multi-centric prospective randomized openlabel study aims to assess the benefits of IgRT versus AP as PP in patients with secondary antibody deficiencies.

Study Overview

• Status: Not yet recruiting
• Conditions: B Cell Lymphoma; Antibiotic Prophylaxis; Immunoglobulin Therapy; B Cell Acute Lymphoblastic Leukemia (B-ALL); Chimeric Antigen Receptor T-cell Therapy
• Intervention / Treatment: Drug: Immunoglobulin; Drug: antibiotic prophylaxis

• Study Type: Interventional
• Enrollment (Estimated): 228
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, MD PhD; Phone Number: +33 +33 1 42 49 97 42; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Florence Rabian, MD; Phone Number: +33 +33 1 42 38 51 27; Email: florence.rabian@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 16-80 years at inclusion
2. B-cell acute lymphoblastic leukemia or a B-cell lymphoma
3. With gamma globulins <4g/L at the time of screening
4. Receiving CD19-targeted autologous CAR-T cells (with AMM in their indication)
5. Patients with childbearing potential* should have reliable contraception for the all duration of the study and another 12 months after CAR-T infusion.
6. Contraceptive measures for concerned patients
7. Informed consent signed by patient or legal representatives

Exclusion Criteria:

1. Any medical history of intolerance to intravenous immunoglobulin
2. With renal failure calculated glomerular filtrate rate <30 mL / min;
3. With hepatic failure or hepatitis or bilirubin> 3 times the upper limit of normal, Serum ALT/AST >=5N
4. With existing serious acute infection
5. Contraindication to immunoglobulin or to prophylactic antibiotherapy administered in this clinical trial
6. No health insurance coverage
7. Females who are pregnant or breastfeeding
8. Participation in another interventional study or being

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunoglobulin Replacement therapy	Drug: Immunoglobulin; IgRT 0.4g/Kg IV every 4 weeks for 12 months
Active Comparator: Antibiotic prophylaxis	Drug: antibiotic prophylaxis; PA following each center's guidelines, for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of recurrent infections	Defined by at least 2 episodes requiring a curative systemic antibiotic treatment	At 12 months
Occurrence of a severe infection	Defined by the need of hospitalization	At 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative hazard of severe infections	requiring hospitalization	Up to 12 months
Infection-free survival rate		Up to 12 months
Occurrence of COVID19 infection		Up to 12 months
Cumulative incidence of readmissions due to infectious episode after hospital discharge following the infusion of CART cells		Up to 12 months
Incidence of adverse events due to IgRT and/or PA		Up to 12 months
Dosage of immune markers	IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts, at lymphodepletion	Up to 12 months
Dosage of immune markers	IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts	At 1 month
Dosage of immune markers	IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts	At 3 months
Dosage of immune markers	IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts	At 6 months
Dosage of immune markers	IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts	At 9 months
Dosage of immune markers	IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts	At 12 months
Quality of life assessment	EQ5D5L : standardized measure of health-related quality of life assessing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D-5L index score typically ranges from values below 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set. Higher scores indicate better health-related quality of life.	At 3 months
Quality of life assessment	EQ5D5L : standardized measure of health-related quality of life assessing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D-5L index score typically ranges from values below 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set. Higher scores indicate better health-related quality of life.	At 6 months
Quality of life assessment	EQ5D5L : standardized measure of health-related quality of life assessing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D-5L index score typically ranges from values below 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set. Higher scores indicate better health-related quality of life.	At 9 months
Quality of life assessment	EQ5D5L : standardized measure of health-related quality of life assessing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D-5L index score typically ranges from values below 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set. Higher scores indicate better health-related quality of life.	At 12 months
Quality of life assessment	EORTC QLQ-C30 : cancer-specific questionnaire designed to assess health-related quality of life in patients with cancer. Scores are linearly transformed to a 0-100 scale. For the Global Health Status/Quality of Life scale and the functional scales, higher scores indicate better quality of life and functioning. For symptom scales, higher scores indicate greater symptom burden and poorer health status.	At 3 months
Quality of life assessment	EORTC QLQ-C30 : cancer-specific questionnaire designed to assess health-related quality of life in patients with cancer. Scores are linearly transformed to a 0-100 scale. For the Global Health Status/Quality of Life scale and the functional scales, higher scores indicate better quality of life and functioning. For symptom scales, higher scores indicate greater symptom burden and poorer health status.	At 6 months
Quality of life assessment	EORTC QLQ-C30 : cancer-specific questionnaire designed to assess health-related quality of life in patients with cancer. Scores are linearly transformed to a 0-100 scale. For the Global Health Status/Quality of Life scale and the functional scales, higher scores indicate better quality of life and functioning. For symptom scales, higher scores indicate greater symptom burden and poorer health status.	At 9 months
Quality of life assessment	EORTC QLQ-C30 : cancer-specific questionnaire designed to assess health-related quality of life in patients with cancer. Scores are linearly transformed to a 0-100 scale. For the Global Health Status/Quality of Life scale and the functional scales, higher scores indicate better quality of life and functioning. For symptom scales, higher scores indicate greater symptom burden and poorer health status.	At 12 months
Incremental Cost-Effectiveness Ratio (ICER)		Up to 12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: July 3, 2026
• First Submitted That Met QC Criteria: August 4, 2026
• First Posted (Actual): August 10, 2026

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 4, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Burkitt Lymphoma; Amino Acids, Peptides, and Proteins; Proteins; Therapeutics; Drug Therapy; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Chemoprevention; Premedication; Immunoglobulins; Antibiotic Prophylaxis
• Other Study ID Numbers: APHP241013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No