Single Arm Pilot Trial of Letermovir for CMV Prophy in CAR T Cell

Open Label Single Arm Pilot Trial of Letermovir for Cytomegalovirus Prophylaxis After Axicabtagene Ciloleucel Therapy

The goal of this clinical research study is to learn if a drug called Letermovir can help to prevent CMV reactivation.

Study Overview

• Status: Recruiting
• Conditions: Cell Therapy
• Intervention / Treatment: Drug: Letermovir

Detailed Description

Primary Objective:

Estimate the probabilities at days d = +28 and +98 following CAR T cell infusion, among patients alive at the day of evaluation, of CMV reactivation in CMV seropositive patients receiving letermovir for CMV prophylaxis after standard of care (SOC) axicabtagene ciloleucel (AXI-CEL) therapy, using the cutoff CMV DNA qPCR > c for c = 400 and 1000 IU/mL to define CMV reactivation, for a total of four (d, c) combinations.

Secondary Objectives:

Estimate overall survival probabilities at days+28, +98, and +364 following CAR T cell infusion of CMV seropositive patients receiving letermovir for CMV prophylaxis after SOC AXI-CEL therapy.

Describe the tolerability of letermovir during the period of CMV prophylaxis after SOC AXI-CEL therapy in CMV seropositive patients at high risk for CMV reactivation.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: George Chen, MD; Phone Number: (713) 792-3630; Email: glchen1@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: George Chen, MD; Phone Number: 713-792-3630; Email: glchen1@mdanderson.org
      • Principal Investigator: George Chen, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years of age.
2. Have an ECOG performance status of 0 or 1.
3. The participant must be scheduled for SOC AXI-CEL.
4. The participant must be seropositive for CMV (defined as having anti-CMV IgG antibodies)
5. Creatinine clearance > 10 mL/min
6. Child Pugh class A or B if liver disease is present.
7. Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately.
8. Participant must understand the investigational nature of this study and sign an Institutional Review Board approved written informed consent form prior to receiving any study related procedure.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection not responding to treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
2. Female participants who are pregnant or breastfeeding.
3. Unwilling or unable to follow protocol requirements.
4. Planned to receive any other anti-CMV therapy such as high dose acyclovir (500 mg/m2/dose intravenously every 8 hours or 800 mg orally 4 times a day) or high dose valacyclovir (2 grams three to four times daily or 2 grams three times daily) for the prophylaxis of CMV reactivation. Acyclovir or valacyclovir at lower doses for the prevention of HSV and VZV are allowed.
5. Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug.
6. Evidence for CMV infection defined as any positive CMV DNA qPCR test within 1 week prior to starting letermovir.
7. Child Pugh class C liver disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Open label Single arm: Letermovir; Participants will be identified/recruited/screened from the Lymphoma and Stem Cell Transplantation and Cellular Therapy services at MD Anderson Cancer Center.	Drug: Letermovir; Given by mouth or intravenously

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: George Chen, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: August 26, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 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: 2023-0828; NCI-2024-07402 (Other Identifier: NCI-CTRP Clinical Trials Registry)

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