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

M.D. Anderson Cancer Center

Status: Enrolling

Conditions: Hematopoietic Cell Transplant; Cytomegalovirus Cell Mediated Immunity

Treatments: Drug: Letermovir; Procedure: Hematopoietic Cell Transplant

Study type: Interventional

Funder types: Other

Identifiers

NCT06639854

2024-1144

NCI-2024-08626 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 105 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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105 participants in 2 patient groups

Interrupted letermovir prophylaxis

Experimental group

Description:

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.

Treatment:

Procedure: Hematopoietic Cell Transplant

Drug: Letermovir

Standard letermovir prophylaxis

Experimental group

Description:

Participants assigned to the standard care group, you will receive treatment with letermovir every day to prevent CMV infection.

Treatment:

Procedure: Hematopoietic Cell Transplant

Drug: Letermovir