The Use of Cytomegalovirus Cell Mediated Immunity to Optimize the Duration of Letermovir Prophylaxis in Hematopoietic Cell Transplant Recipients

The goal of this laboratory research study is to learn if interrupting a patient's letermovir dosing based on their immune system response can help HSC transplant patients avoid post-treatment CMV infections better than taking letermovir every day without interruption.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic Cell Transplant; Cytomegalovirus Cell Mediated Immunity
• Intervention / Treatment: Procedure: Hematopoietic Cell Transplant; Drug: Letermovir

Detailed Description

Primary Objective

•To compare the proportion of CS-CMVi in allo-HCT recipients who had interrupted letermovir prophylaxis based on CMV CMI or extended duration of letermovir prophylaxis up to 200 days post transplantation.

Secondary Objectives

• To compare the proportion of CS-CMVi in HCT recipients who had interrupted letermovir prophylaxis based on CMV CMI or extended duration of letermovir prophylaxis at 365 days post transplantation.
• To compare the overall use of letermovir in HCT recipients in both arms.
• To compare CMV CMI in HCT recipients in both arms.
• To compare all-cause mortality and nonrelapse mortality between the 2 arms at day +200 and day +365.
• Healthcare expenditures for letermovir use and TCIP for both arms from day +100 to day +200.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fareed Khawaja, MBBS; Phone Number: (281) 610-0253; Email: fkhawaja@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Fareed Khawaja, MBBS; Phone Number: 281-610-0253; Email: fkhawaja@mdanderson.org
      • Principal Investigator: Fareed Khawaja, MBBS

Participation Criteria

Eligibility Criteria

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

Study Population

MD Anderson Cancer Center

Description

Inclusion criteria

1. Allogeneic HCT recipients with positive CMV serostatus
2. On letermovir prophylaxis at day 90 post transplant (+/- 7 days)

3. At high risk for CMV reactivation after day +100:

   1. Prior or active graft versus host disease requiring systemic steroids
   2. Mismatch stem cell donor (includes haploidentical, mismatch unrelated donor (MMUD), match related donor with at least one mismatch at one of the three specified HLA gene loci (HLA-A, HLA-B, or HLA-DR) and cord donor recipients)
   3. Received T cell depletion or anti thymoglobulin during conditioning
   4. CMV reactivation prior to day 100 post transplant
   5. On steroids at any dose within 2 weeks of enrollment

Exclusion criteria

1. Patients under the age of 18
2. Patients are discharged from our institution and unwilling to come back for follow up
3. Patients are actively undergoing treatment for CS-CMVi at time of screening. Prior CS-CMVi is not an exclusion from study.
4. Patients are allergic or intolerant to letermovir or have history of letermovir resistant CMV infection.
5. Not able to procure letermovir for extended prophylaxis beyond day +100.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interrupted letermovir prophylaxis; Participants assigned to the investigational group, you will also receive letermovir at first, but depending on the result of the study blood tests, your dose may be paused as long as your immune system shows an immune response against CMV.	Procedure: Hematopoietic Cell Transplant; Participants choices may include to receive standard post-transplant virus prevention with letermovir or other standard drugs without being part of this study. Participants may choose to receive other investigational therapy, if available. These alternative treatments have risks and benefits that may be the same or different than those in this research study.; Drug: Letermovir; Given by PO
Experimental: Standard letermovir prophylaxis; Participants assigned to the standard care group, you will receive treatment with letermovir every day to prevent CMV infection.	Procedure: Hematopoietic Cell Transplant; Participants choices may include to receive standard post-transplant virus prevention with letermovir or other standard drugs without being part of this study. Participants may choose to receive other investigational therapy, if available. These alternative treatments have risks and benefits that may be the same or different than those in this research study.; Drug: Letermovir; Given by PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Adverse Events (AEs).	Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0	Through study completion; an average of 1 year.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Fareed Khawaja, MBBS, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 10, 2024
• First Submitted That Met QC Criteria: October 10, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• 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: 2024-1144; NCI-2024-08626 (Other Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

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