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

NCT07754682 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: APHP241013
• Study Type: interventional
• Target: 228
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Antibiotic Prophylaxis; Chimeric Antigen Receptor T-cell Therapy; B Cell Lymphoma; Immunoglobulin Therapy; B Cell Acute Lymphoblastic Leukemia (B-ALL)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (20)

• Cumulative hazard of severe infections

  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

Study Arms (2)

Immunoglobulin Replacement therapy

EXPERIMENTAL

Drug: Immunoglobulin

Antibiotic prophylaxis

ACTIVE COMPARATOR

Drug: antibiotic prophylaxis

Interventions

Immunoglobulin DRUG

IgRT 0.4g/Kg IV every 4 weeks for 12 months

Immunoglobulin Replacement therapy

antibiotic prophylaxis DRUG

PA following each center's guidelines, for 12 months

Antibiotic prophylaxis

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, B-Cell

Interventions

Immunoglobulins; Antibiotic Prophylaxis

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chemoprevention; Drug Therapy; Therapeutics; Premedication

Central Study Contacts

Florence Rabian, MD

CONTACT

+33 1 42 38 51 27; florence.rabian@aphp.fr

Jérôme Lambert, MD PhD

CONTACT

+33 1 42 49 97 42; jerome.lambert@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III randomized two-parallel arms, open-label multicentric design in patients treated by CD19-targeted CAR-T Cells for a B-ALL or a BCL, randomly allocated in a 1:1 ratio to receive either IgRT or PA.

Study Record Dates

• First Submitted: July 3, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: August 10, 2026

Record last verified: 2026-08