Letermovir + CMV-TCIP for Cytomegalovirus After Stem Cell Transplant

Overseen By University of California Irvine Medical

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Irvine

Must not be taking: Ganciclovir, Valganciclovir, Foscarnet, others

Disqualifiers: CMV end-organ disease, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to manage cytomegalovirus (CMV) in patients who have undergone a stem cell transplant. It tests whether a special blood test, the CMV T Cell Immunity Panel (CMV-TCIP), can determine the duration of CMV protection needed after transplantation. The trial uses Letermovir (Prevymis), a medication for CMV, and targets individuals who are CMV-positive but have no detectable CMV in their blood. Participants should not have recently taken certain CMV medications and must have stable health conditions. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain antiviral medications like Ganciclovir, Valganciclovir, Foscarnet, and others listed in the exclusion criteria before and during the study. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Letermovir is generally safe and effective in preventing CMV (cytomegalovirus) infections after a stem cell transplant. It works well for both adults and children over six months old.

Letermovir has been widely used in transplant patients, providing extensive information about its safety. It helps prevent serious CMV infections after transplants. In one study, only about 11% of children experienced CMV reactivation after treatment with Letermovir, indicating its effectiveness.

Specific safety data for CMV-TCIP is not yet available. As this trial is in an early phase, the treatment shows promise, but its safety is not fully known.

Overall, Letermovir has a strong safety record. CMV-TCIP is still under study, so more information is needed to fully understand its safety in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CMV-TCIP for cytomegalovirus (CMV) after stem cell transplants because it offers a new approach compared to existing antiviral drugs like ganciclovir, foscarnet, and cidofovir. Unlike these standard treatments, which often suppress CMV by inhibiting viral DNA replication, CMV-TCIP works by leveraging T-cell immunotherapy to boost the body's own immune response against the virus. This innovative mechanism has the potential to provide a more targeted and effective defense with possibly fewer side effects, as it strengthens the immune system rather than directly attacking the virus.

What evidence suggests that Letermovir + CMV-TCIP might be an effective treatment for Cytomegalovirus?

Research has shown that Letermovir reduces the risk of complications and death from CMV (Cytomegalovirus) in patients who have undergone stem cell transplants. Studies indicate that it significantly decreases CMV-related problems and improves survival rates. Using Letermovir as a preventive measure also leads to better outcomes after certain types of stem cell transplants.

In this trial, researchers are studying the CMV-TCIP treatment alongside Letermovir. The goal is to use a specific test (CMV-TCIP) to determine how long a patient should continue taking Letermovir. This test evaluates the body's immune response to CMV, potentially allowing for a customized treatment duration for each patient. ^{2 4 5 6 7}

Who Is on the Research Team?

Piyanuch Kongtim, MD,PhD

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had a stem cell transplant from a CMV-positive donor or are themselves CMV-positive. They must have good organ function, no recent severe infections, and not be taking certain antiviral drugs. It's not for those with recent CMV disease or allergies to Letermovir.

Inclusion Criteria

Have undetectable CMV DNA from a plasma sample collected within 5 days prior to enrollment

I am able to care for myself but may not be able to do active work.

I had a stem cell transplant less than 28 days ago.

Exclusion Criteria

I had a CMV infection affecting my organs within the last 6 months.

Received within 7 days prior to screening or plans to receive during the study any of the following: Ganciclovir, Valganciclovir, Foscarnet, Acyclovir (> 3200 mg PO per day or > 25 mg/kg IV per day), Valacyclovir (> 3000 mg/day), 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 on the day of randomization, Requires mechanical ventilation or is hemodynamically unstable at the time of randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CMV-specific T cell immunity directed letermovir prophylaxis guided by CMV-TCIP assay

14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

38 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CMV-TCIP
• Letermovir

Trial Overview The study tests if monitoring the immune response to CMV (using the CMV-TCIP assay) can guide how long patients should take Letermovir as prevention against CMV after an allogeneic stem cell transplant.

How Is the Trial Designed?

Group I: AHCT recipients Experimental Treatment 3 Interventions

CMV-TCIP is already approved in United States for the following indications:

Approved in United States as Prevymis for:

• Prevention of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients undergoing allogeneic hematopoietic stem cell transplant

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Eurofins Viracor

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

In a study of 38 CMV seropositive patients undergoing haploidentical or mismatched unrelated donor allogeneic hematopoietic cell transplantation, letermovir (LET) significantly reduced the incidence of CMV infection to 5% compared to 53% with high-dose valacyclovir (HDV).

LET also decreased the need for CMV treatment by day +100 (5% vs. 37%) and improved median CMV event-free survival, indicating its efficacy as a prophylactic treatment in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir vs. high-dose valacyclovir for cytomegalovirus prophylaxis following haploidentical or mismatched unrelated donor allogeneic hematopoietic cell transplantation receiving post-transplant cyclophosphamide. Freyer, CW., Carulli, A., Gier, S., et al.[2022]

Letermovir, a new antiviral drug, has been shown to significantly suppress cytomegalovirus (CMV) infection in patients undergoing hematopoietic stem cell transplantation (HSCT), leading to improved overall survival rates in a phase III clinical trial.

Despite the effectiveness of preemptive therapy in managing CMV, it does not reduce non-relapse mortality rates, highlighting the need for continued development of vaccines and cell therapies for CMV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cytomegalovirus infections following allogeneic hematopoietic stem cell transplantation: prophylaxis and treatment]. Katayama, Y., Iwato, K.[2019]

Letermovir, an anti-CMV drug, was successfully used to treat ganciclovir-resistant CMV colitis in a heart transplant recipient, demonstrating its potential as a curative option.

In a second case, while letermovir was used as pre-emptive therapy for CMV reactivation, it did not prevent CMV esophagitis, indicating that while effective for secondary prophylaxis, it may not always prevent all forms of CMV-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir use to treat complex cytomegalovirus reactivations in two heart transplant recipients. Boignard, A., Augier, C., Kheng, M., et al.[2022]

In a study of 80 CMV-seropositive adult patients receiving letermovir as secondary prophylaxis after hematopoietic cell transplantation, the treatment was well tolerated and showed a low rate of breakthrough infections (5.5%), indicating its potential effectiveness in preventing CMV reactivation in high-risk patients.

Letermovir was administered for a median of 118 days, providing a crucial bridge between initial CMV treatment and immune recovery, although further research is needed to confirm these findings and assess long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir for Secondary Prophylaxis of Cytomegalovirus Infection and Disease after Allogeneic Hematopoietic Cell Transplantation: Results from the French Compassionate Program. Robin, C., Thiebaut, A., Alain, S., et al.[2021]

In a study of 6 transplant patients treated with letermovir for refractory CMV infection, 3 asymptomatic patients showed a significant decrease in viral load to below 200 IU/mL, indicating potential efficacy of the drug.

No treatment-related adverse effects were reported, suggesting that letermovir may be a safe option for treating CMV infections, although its effectiveness appears to vary and may be enhanced when used alongside other antiviral medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir as Salvage Therapy for Cytomegalovirus Infection in Transplant Recipients. Phoompoung, P., Ferreira, VH., Tikkanen, J., et al.[2023]

In a phase 3 trial involving 565 CMV-seropositive transplant recipients, letermovir significantly reduced the risk of clinically significant CMV infection compared to placebo, with 37.5% of patients on letermovir experiencing infection versus 60.6% on placebo (P<0.001).

The safety profile of letermovir was comparable to placebo, with similar rates of adverse events, and it showed a lower all-cause mortality rate at 48 weeks (20.9% for letermovir vs. 25.5% for placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. Marty, FM., Ljungman, P., Chemaly, RF., et al.[2022]

Letermovir is the first new drug approved for preventing cytomegalovirus (CMV) in transplant patients since 2003, but its effectiveness in treating existing CMV infections is still uncertain due to a potential low barrier to resistance.

Maribavir shows promise as a preemptive treatment for CMV, with ongoing studies needed to confirm its efficacy, particularly in patients with resistant infections, and both letermovir and maribavir have unique mechanisms that reduce the risk of cross-resistance and do not cause myelotoxicity or nephrotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir and Maribavir for the Treatment and Prevention of Cytomegalovirus Infection in Solid Organ and Stem Cell Transplant Recipients. Imlay, HN., Kaul, DR.[2021]

Letermovir, a new anti-CMV drug with fewer side effects, was successfully used off-label to treat a heart transplant recipient with ganciclovir-resistant CMV colitis, highlighting its potential as an alternative treatment.

The case suggests that monitoring CMV-pp65 antigenemia levels could be a useful additional marker for assessing the efficacy of letermovir treatment, alongside traditional CMV-DNA PCR levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment with Letermovir in a Heart Transplant Recipient with UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Colitis and Viremia. Yanase, T., Hatano, M., Bujo, C., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10918401/

Real-Life Data on the Efficacy and Safety of Letermovir for ... In this study, we report on our first experience with LMV prophylaxis in 93 CMV-seropositive adult patients receiving HSCT in our center.

2. astctjournal.org astctjournal.org/article/S2666-6367(25)01268-0/fulltext

Updated Cytomegalovirus Guidelines in Hematopoietic ... This eleventh topic in the series focuses on new antiviral treatments for CMV, expanded indications of existing antiviral therapy for the prevention of CMV,

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11263243/

Final Results of Post-Marketing Surveillance in Japan We report the final results of a preemptive therapy to assess the safety profile and effectiveness of letermovir for cytomegalovirus (CMV) ...

4. merckconnect.com merckconnect.com/prevymis/kidney-transplant-endpoint-results/

Study results in adult kidney transplant patients PREVYMIS was noninferior to valganciclovir in preventing CMV disease. Incidence of CMV disease through Week 52 (~365 days) post-transplant (OF approach).

5. journalofinfection.com journalofinfection.com/article/S0163-4453(24)00154-3/fulltext

Real-world experience with letermovir for cytomegalovirus ... Real-world experience with letermovir for cytomegalovirus-prophylaxis after allogeneic hematopoietic cell transplantation: A multi-centre observational study

6. prevymis.com prevymis.com/

Official Consumer Site for PREVYMIS® (letermovir) PREVYMIS is a prescription medicine used to help prevent Cytomegalovirus (CMV) infection and disease in adults and children 6 months and older.

7. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/prevymis

Prevymis | European Medicines Agency (EMA) Supportive data from this study indicated that around 11% (6 out of 56) of the treated children had signs of CMV becoming active 24 weeks after the stem cell ...