Incidence and Risks Factors of CMV Reactivation in Patients Receiving of CAR-T Cells for Acute Leukemia and Lymphoma Relapse, a Cohort Study Analysis

Recruiting

• Conditions: B Cell Lymphoma; Acute Leukemia; Cytomegalovirus Infections

• Registration Number: NCT06058858
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Letermovir is approved for the primary prevention of Cytomegalovirus (CMV) reactivation and infection in hematopoietic stem cell transplant recipients. Letermovir may be beneficial in other clinical presentation where CMV reactivates and may alter clinical outcomes. Recently Chimeric Antigen Receptor (CAR) T cells have been used for the treatment of refractory acute leukemia and B cell lymphoma. Reactivation of chronic viral infections, in particular those belonging to the Herpesviridae family can therefore be observed following CAR-T cells treatment.According to first reports, Cytomegalovirus seems to be the main virus detected. Uncontrolled CMV reactivation leads to CMV disease requiring the use of antiviral drugs associated with either hematological toxicity (ganciclovir) or renal toxicity (foscarnet) and is usually associated with poor outcomes. In addition, CMV interplays with the immune system and decreases the immunosurveillance of tumor cells and facilitates the growth or reactivation of other opportunistic infections. Therefore, CMV reactivation could also impact the outcome of CART cells treatment by increasing the existing risk of opportunistic infections in CART cells recipients and thus by increasing morbidity, length stay or require intensive care. Imbalance of the immune system usually correlates with reactivation of persistent virus like Torquetenovirus (TTV), redondovirus or pegivirus found more frequently in Hematopoietic stem-cell transplantation (HSCT) patients or patients requiring intensive care. Whether reactivations of those persistent viruses are associated or precede CMV reactivation deserve careful investigation to identify as early as possible patients at high risk and who could benefit from antiviral preventive treatment.

The objective of this trial is to determine the incidence of CMV reactivation within 3 months after infusion of CAR-T cells in CMV seropositive patients with refractory acute leukemia or B-cell lymphoma.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-22
• Study First Submitted QC: 2023-09-22
• Study First Posted: 2023-09-28
• Study Start: 2024-04-17
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-15
• Last Update Posted: 2024-07-17
• Primary Completion: 2025-04-17
• Study Completion: 2025-04-17

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

Not provided

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Exclusion Criteria

• CMV seronegative patients
• Lack of affiliation to a social security scheme (as a beneficiary or assignee)
• Patients under guardianship / curatorship
• Patient under AME (state medical aid)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rate of CMV reactivation	Up to 3 months after inclusion	Rate of CMV reactivation occurring within the first 3 months after CAR-T-cell infusion in paediatric and adult patients treated for refractory B cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL).

Secondary Outcome Measures

Name	Time	Method
Rate of anellovirus infection	Up to 3 months
Rate of redondovirus infection	Up to 3 months
Detection of mutations in the CMV DNA polymerase gene in patients under acyclovir or valacyclovir prophylaxis	Up to 3 months
Cost of illness of CMV disease	Up to 3 months	Illness of CMV disease is defined by prolonged initial hospitalization, additional hospitalizations, increased surveillance in case of reactivation (consults and biological sampling), treatments)
Rate of CMV disease	Up to 3 months
Rate of pegivirus infection	Up to 3 months
Correlation between CMV reactivation and the expansion of CAR-T cells	Up to 3 months
Correlation between CMV reactivation and other early viral persistent reactivations (anellovirus, pegivirus, redondovirus)	Up to 3 months
Rate of CMV reactivation in patients with acute leukemia	Up to 3 months
Rate of CMV reactivation in patients with lymphoma	Up to 3 months
Health related quality of life (HRQL)) of the study population with or without CMV activation	Up to 3 months	EQ-5D-5L scale (adult) EQ-5D-Y scale (child) First part describes 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) Second part is a visual analogue scale with a score varying from 0 to 100; the higher the score the better the state of health.
Correlation between CMV reactivation and the occurrence of other bacterial or fungal infections	Up to 3 months

Trial Locations

Locations (3)

Hopital Robert Debré - APHP; 🇫🇷 Paris, France

Hopital Saint-Louis - APHP - Service d'éhamotologie - oncologie; 🇫🇷 Paris, France

Hopital Saint Louis - APHP - Service d'hématologie " Unité Adolescents et jeunes adultes "; 🇫🇷 Paris, France