Using Letermovir to prevent CMV reactivation in CAR T cell therapy patients

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

This study is testing if the drug Letermovir can help prevent CMV reactivation in patients who have received CAR T cell therapy and are already positive for the virus.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: CAR T
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06575374 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of Letermovir in preventing cytomegalovirus (CMV) reactivation in patients who are seropositive for CMV and undergoing CAR T cell therapy with axicabtagene ciloleucel (AXI-CEL). The study will assess the probabilities of CMV reactivation at specific time points following treatment and will also evaluate overall survival rates and the tolerability of Letermovir during the prophylaxis period. Participants will be monitored for CMV DNA levels to determine reactivation and will provide informed consent before participating.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who are CMV seropositive and scheduled to receive SOC AXI-CEL therapy.

Not a fit: Patients who are CMV seronegative or those with uncontrolled intercurrent illnesses may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce the risk of CMV reactivation in patients receiving CAR T cell therapy, improving their overall outcomes.

How similar studies have performed: While the use of Letermovir has been explored in other contexts, this specific application in CAR T cell therapy is novel and has not been extensively tested.

Eligibility criteria

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.

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: George Chen, MD — M.D. Anderson Cancer Center
• Study coordinator: George Chen, MD

Conditions Cell Therapy