Clinical trial NCT06058858: Incidence and Risks Factors of CMV Reactivation in Patients Receiving of CAR-T Cells for Acute Leukemia and Lymphoma Relapse, a Cohort Study Analysis
Official title: Incidence and Risks Factors of CMV Reactivation in Patients Receiving of CAR-T Cells for Acute Leukemia and Lymphoma Relapse, a Cohort Study Analysis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cytomegalovirus Infections
Acute Leukemia
B Cell Lymphoma
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-09-28
Enrollment: 250
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Paediatric and adult patient treated by CAR-T cells

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Rate of CMV reactivation
timeFrame: Up to 3 months after inclusion
Secondary outcomes:
measure: Rate of CMV disease
timeFrame: Up to 3 months
measure: Rate of anellovirus infection
timeFrame: Up to 3 months
measure: Rate of pegivirus infection
timeFrame: Up to 3 months
measure: Rate of redondovirus infection
timeFrame: Up to 3 months
measure: Correlation between CMV reactivation and the occurrence of other bacterial or fungal infections
timeFrame: Up to 3 months
measure: Correlation between CMV reactivation and the expansion of CAR-T cells
timeFrame: Up to 3 months
measure: Correlation between CMV reactivation and other early viral persistent reactivations (anellovirus, pegivirus, redondovirus)
timeFrame: Up to 3 months
measure: Rate of CMV reactivation in patients with acute leukemia
timeFrame: Up to 3 months
measure: Rate of CMV reactivation in patients with lymphoma
timeFrame: Up to 3 months
measure: Detection of mutations in the CMV DNA polymerase gene in patients under acyclovir or valacyclovir prophylaxis
timeFrame: Up to 3 months
measure: Health related quality of life (HRQL)) of the study population with or without CMV activation
timeFrame: Up to 3 months
measure: Cost of illness of CMV disease
timeFrame: Up to 3 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Robert Debré - APHP
city: Paris
country: France
facility: Hopital Saint Louis - APHP - Service d'hématologie " Unité Adolescents et jeunes adultes "
city: Paris
country: France
facility: Hopital Saint-Louis - APHP - Service d'éhamotologie - oncologie
Study officials:
References: