CMV-TCIP Directed Letermovir Prophylaxis After Allo-SCT

Prospective Evaluation of Efficacy of CMV-specific T Cell Immunity (CMV-TCIP) Directed Letermovir Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

This is a phase 2, prospective cohort clinical trial evaluating the utilization of CMV T Cell Immunity Panel (CMV-TCIP) assay to guide the duration of primary CMV prophylaxis in CMV-seropositive recipients of allogeneic stem cell transplant or recipients receiving a stem cell graft from a CMV serology positive donor.

Study Overview

• Status: Recruiting
• Conditions: CMV; Allogeneic Stem Cell Transplantation
• Intervention / Treatment: Drug: Letermovir; Device: CMV T Cell Immunity Panel (CMV-TCIP); Diagnostic test: CMV DNA PCR

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chao Family Comprehensive Cancer Center University of California, Irvine; Phone Number: 1-877-827-8839; Email: ucstudy@uci.edu
• Study Contact Backup: Name: University of California Irvine Medical

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Chao Family Comprehensive Cancer Center, University of California Irvine
      • Contact: Piyanuch Kongtim, MD, PhD; Phone Number: 877-827-8839; Email: ucstudy@uci.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ≥ 18 years of age on the day of signing informed consent.
• Karnofsky performance >70%
• Have documented seropositivity for CMV (either donor or recipient CMV IgG seropositivity) before AHCT.
• Eligible for AHCT from an HLA-matched related, matched unrelated, mismatched unrelated or haploidentical donor using either bone marrow or peripheral blood stem cells.
• Have undetectable CMV DNA from a plasma sample collected within 5 days prior to enrollment.
• Must be within Day-10 thru Day+28 days of planned HSCT at the time of enrollment.
• Be able to comply with medical recommendations or follow-up.

• Has adequate organ functions determined by

  1. Serum creatinine clearance ≥50 ml/min (calculated with Cockroft-Gault formula).
  2. Bilirubin ≤1.5 mg/dl except for Gilbert's disease.
  3. ALT or AST ≤200 IU/ml for adults.
  4. Conjugated (direct) bilirubin < 2x upper limit of normal.
  5. Left ventricular ejection fraction ≥40%.
  6. Diffusing capacity for carbon monoxide (DLCO) ≥ 50% predicted corrected for hemoglobin.

Exclusion Criteria:

• Has a history of CMV end-organ disease or CS-CMVi within 6 months prior to enrollment.

• Received within 7 days prior to screening or plans to receive during the study any of the following:

  1. Ganciclovir
  2. Valganciclovir
  3. Foscarnet
  4. Acyclovir (> 3200 mg PO per day or > 25 mg/kg IV per day)
  5. Valacyclovir (> 3000 mg/day)
  6. Famciclovir (> 1500 mg/day)
• Received within 30 days prior to screening or plans to receive during the study any of the following drugs: cidofovir, CMV hyper-immune globulin, any investigational CMV antiviral agent/biologic therapy.
• Has suspected or known hypersensitivity to active or inactive ingredients of letermovir formulations.
• Has an uncontrolled infection
• Requires mechanical ventilation or is hemodynamically unstable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: AHCT recipients

Drug: Letermovir; Subjects will receive 14 weeks of letermovir prophylaxis at standard recommended dose follow by CMV-TCIP-directed extended prophylaxis.; Device: CMV T Cell Immunity Panel (CMV-TCIP); Viracor CMV-TCIP assay to measure how a person's immune system responds to CMV. Viracor CMV-TCIP will be measured monthly, starting at week 14, until positive, then at week 30 and 52.; Diagnostic test: CMV DNA PCR; Plasma level of CMV DNA PCR will be measured at enrollment and at least weekly through week 30, then at least every 2 weeks through week 52 of transplant if no GVHD or CMV reactivation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of clinically significant cytomegalovirus infection (CS-CMVi) at 52 weeks after transplant	Number of patients who develop CS-CMVi within 52 weeks after receiving a transplant	1 year after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of CMV disease at 52 weeks after transplant	Number of patients who develop CMV disease within 52 weeks after receiving a transplant	1 year after transplant
Cumulative incidence of CMV related death at 52 weeks	Number of patients who die from complications directly attributable to CMV infection within 52 weeks	1 year after transplant
Overall Survival at 1 year after transplant	Number of patients who survive beyond 1 year after transplant	1 year after transplant
Positive predictive value of CMV-TCIP assay after transplant in predicting CS-CMVi protection	Positive predictive value of CMV-TCIP assay at 14 weeks after transplant in predicting CS-CMVi protection through 1 year after transplant in patients who had letermovir discontinuation	1 year after transplant

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: Eurofins Viracor
• Investigators: Principal Investigator: Piyanuch Kongtim, MD,PhD, Chao Family Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: June 5, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: July 3, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: CMV reactivation; Letermovir; Allogeneic stem cell transplantation; CMV T Cell Immunity Panel
• Additional Relevant MeSH Terms: Poly(ADP-ribose) Polymerase Inhibitors; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiviral Agents; Letermovir
• Other Study ID Numbers: 4005; UCI 22-188 (Other Identifier: UCI)

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: Yes
• product manufactured in and exported from the U.S.: No