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

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.

Study Overview

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

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Jérôme Le Goff, Pr; Phone Number: +33142499493; Email: jerome.legoff@aphp.fr
• Study Contact Backup: Name: Jérôme Lambert, Pr; Phone Number: +33142499742; Email: jerome.lambert@u-paris.fr

Study Locations

• France
  • Paris, France
    • Recruiting
    • Hôpital Robert Debré - APHP
    • Contact: Marie-Emilie Dourthe, MD
  • Paris, France
    • Recruiting
    • Hopital Saint Louis - APHP - Service d'hématologie " Unité Adolescents et jeunes adultes "
    • Contact: Florence Rabian, MD
  • Paris, France
    • Recruiting
    • Hopital Saint-Louis - APHP - Service d'éhamotologie - oncologie
    • Contact: Roberta Di Blasi, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Paediatric and adult patient treated by CAR-T cells

Description

Common inclusion criteria :

• Paediatric (1 to 18 years old) receiving CART-T cells treatment for refractory acute leukemia or B-cell lymphoma
• Adult receiving CART-T cells treatment for refractory acute leukemia or B-cell lymphoma
• CMV seropositive patients

Inclusion criteria : retrospective part

• Provide written non-opposition from the patient signed by investigator
• If the patient is a minor, provide written non-opposition from both parents and child (if age appropriate to collect their non-objection) or child and the legal representative in case only one parent is alive, signed by investigator

Inclusion criteria : prospective part

• Provide written consent form signed by patient and investigator
• If the patient is a minor, provide written consent form signed by investigator and both parents or signed by investigator and the legal representative in case only one parent is alive

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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of CMV reactivation	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).	Up to 3 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of CMV disease		Up to 3 months
Rate of anellovirus infection		Up to 3 months
Rate of pegivirus infection		Up to 3 months
Rate of redondovirus infection		Up to 3 months
Correlation between CMV reactivation and the occurrence of other bacterial or fungal infections		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
Detection of mutations in the CMV DNA polymerase gene in patients under acyclovir or valacyclovir prophylaxis		Up to 3 months
Health related quality of life (HRQL)) of the study population with or without CMV activation	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.	Up to 3 months
Cost of illness of CMV disease	Illness of CMV disease is defined by prolonged initial hospitalization, additional hospitalizations, increased surveillance in case of reactivation (consults and biological sampling), treatments)	Up to 3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2024
• Primary Completion (Estimated): April 17, 2025
• Study Completion (Estimated): April 17, 2025

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; DNA Virus Infections; Herpesviridae Infections; Lymphoma; Leukemia; Acute Disease; Cytomegalovirus Infections
• Other Study ID Numbers: APH211589

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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