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

Acute Leukemia Clinical Trial

— CMV CAR-T  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06058858
• Other study ID #: APH211589
• Status: Not yet recruiting
• Start date: October 1, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: September 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Jérôme Le Goff, Pr
• Phone: +33142499493
• Email: jerome.legoff[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 250
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 100 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemia
• B Cell Lymphoma
• Cytomegalovirus Infections
• Leukemia
• Lymphoma

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rate of CMV disease		Up to 3 months
Secondary	Rate of anellovirus infection		Up to 3 months
Secondary	Rate of pegivirus infection		Up to 3 months
Secondary	Rate of redondovirus infection		Up to 3 months
Secondary	Correlation between CMV reactivation and the occurrence of other bacterial or fungal infections		Up to 3 months
Secondary	Correlation between CMV reactivation and the expansion of CAR-T cells		Up to 3 months
Secondary	Correlation between CMV reactivation and other early viral persistent reactivations (anellovirus, pegivirus, redondovirus)		Up to 3 months
Secondary	Rate of CMV reactivation in patients with acute leukemia		Up to 3 months
Secondary	Rate of CMV reactivation in patients with lymphoma		Up to 3 months
Secondary	Detection of mutations in the CMV DNA polymerase gene in patients under acyclovir or valacyclovir prophylaxis		Up to 3 months
Secondary	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
Secondary	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