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NCT Number: NCT07754682

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

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.

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Key information

Conditions

Chimeric Antigen Receptor T-cell Therapy Antibiotic Prophylaxis B Cell Acute Lymphoblastic Leukemia (B-ALL) B Cell Lymphoma Burkitt Lymphoma DNA Virus Infections Epstein-Barr Virus Infections Hemic and Lymphatic Diseases Herpesviridae Infections Immune System Diseases Immunoglobulin Therapy Immunoproliferative Disorders Infections Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Tumor Virus Infections Virus Diseases

Age range

16 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 16-80 years at inclusion
  • 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

Exclusion criteria

  • 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

Treatment and study plan

Immunoglobulin

Drug

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

Antibiotic Prophylaxis

Drug

PA following each center's guidelines, for 12 months

Primary outcomes

  1. Occurrence of recurrent infections

    Time frame: At 12 months

    Defined by at least 2 episodes requiring a curative systemic antibiotic treatment

  2. Occurrence of a severe infection

    Time frame: At 12 months

    Defined by the need of hospitalization

Secondary outcomes

  1. Cumulative hazard of severe infections

    Time frame: Up to 12 months

    requiring hospitalization

  2. Infection-free survival rate

    Time frame: Up to 12 months

  3. Occurrence of COVID19 infection

    Time frame: Up to 12 months

  4. Cumulative incidence of readmissions due to infectious episode after hospital discharge following the infusion of CART cells

    Time frame: Up to 12 months

  5. Incidence of adverse events due to IgRT and/or PA

    Time frame: Up to 12 months

  6. Dosage of immune markers

    Time frame: Up to 12 months

    IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts, at lymphodepletion

  7. Dosage of immune markers

    Time frame: At 1 month

    IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts

  8. Dosage of immune markers

    Time frame: At 3 months

    IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts

  9. Dosage of immune markers

    Time frame: At 6 months

    IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts

  10. Dosage of immune markers

    Time frame: At 9 months

    IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts

  11. Dosage of immune markers

    Time frame: At 12 months

    IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts

  12. Quality of life assessment

    Time frame: At 3 months

    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.

  13. Quality of life assessment

    Time frame: At 6 months

    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.

  14. Quality of life assessment

    Time frame: At 9 months

    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.

  15. Quality of life assessment

    Time frame: At 12 months

    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.

  16. Quality of life assessment

    Time frame: At 3 months

    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.

  17. Quality of life assessment

    Time frame: At 6 months

    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.

  18. Quality of life assessment

    Time frame: At 9 months

    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.

  19. Quality of life assessment

    Time frame: At 12 months

    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.

  20. Incremental Cost-Effectiveness Ratio (ICER)

    Time frame: Up to 12 months

Study contacts

Contact information is provided by the study sponsor or research team.

Florence Rabian, MD

CONTACT

[email protected]

+33 1 42 38 51 27 ext. +33

Jérôme Lambert, MD PhD

CONTACT

[email protected]

+33 1 42 49 97 42 ext. +33

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

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

Acronym: PREV-CART

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Aug 10, 2026
Registry last updated
Aug 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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