Letermovir for Primary Prophylaxis of Cytomegalovirus Infection After R+HID-HSCT

Efficacy and Safety of Letermovir for Primary Prophylaxis of Cytomegalovirus Infection After HLA-haploidentical Hematopoietic Stem Cell Transplantation

To evaluate the efficacy and safety of primary prophylaxis of CMV reactivation, clinically significant CMV infection with oral letermovir in Chinese R+ haplo-HSCT patients, as well as treatment-related mortality and all-cause mortality within 24 weeks after transplantation. For enrolled patients, Letermovir would be administered at a dose of 480 mg per day (or 240 mg per day in patients taking cyclosporine). The regimen would start between +7~+14d after transplantation. The total duration of dosing was approximately 100 days or 14 weeks.

Study Overview

• Status: Not yet recruiting
• Conditions: The Incidence of Peripheral Blood CMV Activation and Confirmed Clinically Significant CMV Infection Within 24 Weeks After Transplantation
• Intervention / Treatment: Drug: Letermovir

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• (1) Underwent HLA-haploidentical donor HSCT and could receive investigational drug within 28 days of transplantation. (2) have documented seropositivity for CMV (recipient CMV IgG seropositivity [R+]) within 1 year before HSCT., plasma CMV-DNA copy number less than the lower limit of detection within 5 days before enrollment (threshold of 1000 copies/ml in our hospital); (3) Age elder than or equal to 18 years; (4) Informed consent may be signed by themselves. (5) HIV negative, HBV, HCV negative; (6) Informed consent must be signed before the start of the study procedures, and informed consent must be signed by the patient himself or his immediate family. Considering the patient 's condition, if the patient' s signature is unfavorable for disease treatment, the informed consent form should be signed by the legal guardian or the patient 's immediate family member.

Exclusion Criteria:

• Subjects who met any of the following criteria were not enrolled in this study: (1) received a previous allogeneic HSCT; (2) has a history of CMV end-organ disease within 6 months prior to enrollment, or has evidence of CMV viremia from a central or local laboratory at any time prior to enrollment; (3) received within 7 days prior to screening or plans to receive during the study any of the following: ganciclovir, valganciclovir, foscarnet sodium, acyclovir (daily oral dose > 3200 mg, or daily intravenous dose > 25 mg/kg), valacyclovir (daily oral dose > 3000 mg), famciclovir (daily oral dose > 1500 mg); (4) received within 30 days prior to screening or plans to receive during the study any of the following: cidofovir, CMV high-titer gamma globulin, any investigational anti-CMV therapy or biological agent; (5) has severe hepatic insufficiency (defined as Child-Pugh Class C; (6) has serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 xthe upper limit of normal (ULN) or serum total bilirubin > 2.5 x ULN.(7) has end-stage renal impairment with a creatinine clearance less than 10 mL/min. (8) has both moderate hepatic insufficiency AND moderate renal insufficiency; (9) Uncontrolled infection at enrollment; (10) requires mechanical ventilation or is hemodynamically unstable at the time of enrollment; (11) has documented positive results for human immunodeficiency virus antibody (HIVAb), hepatitis C virus antibody (HCV-Ab) with detectable HCV RNA, or hepatitis B surface antigen (HBsAg) within 90 days prior to randomization (12) has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (e.g., lymphomas). (13) Suffering from mental disorders or other conditions and unable to cooperate with the requirements of study treatment and monitoring; 14) unable or unwilling to sign the consent form; 15) pregnant or lactating women; 16) patients with other special conditions assessed as unqualified by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment arm	Drug: Letermovir; For enrolled patients, Letermovir would be administered at a dose of 480 mg per day (or 240 mg per day in patients taking cyclosporine). The regimen would start between +7~+14d after transplantation. The total duration of dosing was approximately 100 days or 14 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CMV reactivation or clinically significant CMV infection incidence	The incidence of peripheral blood cytomegalovirus activation and confirmed clinically significant CMV infection	24 weeks after HSCT

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: HSCT; CMV reactivation; CMV infection
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Letermovir
• Other Study ID Numbers: IIT-CMV-PP-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No