Letermovir for Preventing Infection After Stem Cell Transplant in Blood Cancer

Not currently recruiting at 19 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Pimozide, Ergot alkaloids

Disqualifiers: Pregnancy, Breastfeeding, CMV end organ disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the antiviral drug letermovir can prevent infections caused by cytomegalovirus (CMV) in children and teens who have undergone a stem cell transplant for blood cancer. Stem cell transplants can weaken the immune system, increasing susceptibility to infections like CMV. Letermovir aims to stop CMV from multiplying and causing infection. Children and teens who have already had a stem cell transplant and are CMV-positive might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that certain medications be stopped at least 14 days before starting the study. These include pimozide, ergot alkaloids, and specific statins if you are taking cyclosporine. Check with the trial team to see if your current medications are on this list.

Is there any evidence suggesting that letermovir is likely to be safe for humans?

Research shows that letermovir safely and effectively prevents cytomegalovirus (CMV) infections, especially after stem cell transplants. Studies have found that letermovir is well-tolerated in both children and teenagers. One study demonstrated that using letermovir for a longer period significantly reduced CMV reactivation, from 29.5% to just 3.7%. Moreover, high-risk patients who took the drug as a preventive measure did not experience any CMV reactivation.

Further research confirms that letermovir is very safe. It is considered safer and more effective for preventing CMV than other drugs, like valganciclovir. Overall, letermovir lowers the risk of CMV infections without causing serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for preventing infections after stem cell transplants, which often includes antiviral drugs like ganciclovir or foscarnet, Letermovir targets the CMV virus differently. It works by inhibiting the CMV DNA terminase complex, a novel mechanism of action that prevents the virus from replicating. Researchers are excited about Letermovir because it offers a targeted approach with potentially fewer side effects than current treatments, which can be toxic to the kidneys and bone marrow. Additionally, Letermovir can be administered orally or intravenously, providing flexibility in treatment options for patients.

What evidence suggests that letermovir might be an effective treatment for preventing CMV infection after stem cell transplant?

Research has shown that letermovir, which participants in this trial may receive, helps prevent cytomegalovirus (CMV) infections in individuals who have undergone stem cell transplants. One study found that only 11.1% of patients taking letermovir experienced CMV reactivation by day 100, compared to 82.4% of those who did not take it. Letermovir is also safe for children and effectively prevents CMV from causing complications. Overall, it reduces the chance of the virus spreading, which is crucial when the body's defenses are low after a transplant. ^{6 7 8 9 10}

Who Is on the Research Team?

Caitlin W Elgarten

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and teens (2-18 years old) who weigh at least 18 kg, are CMV sero-positive, and are planning to have a stem cell transplant. They must be healthy enough for the procedure (Lansky/Karnofsky scores > 50), not need dialysis, and have acceptable liver function tests.

Inclusion Criteria

Patient must be CMV sero-positive (i.e., recipient CMV immunoglobulin G positive)

I am between 2 and 17 years old.

My kidneys work well enough and I'm not on dialysis.

Exclusion Criteria

Hypersensitivity to letermovir or any component of the formulation

I cannot take letermovir by mouth.

All patients and/or their parents or legal guardians must sign a written informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive letermovir orally or intravenously once daily starting on day +1 post-transplant for 14 weeks

14 weeks

Weekly visits for blood sample collection

Follow-up

Participants are monitored for CMV infection and other outcomes post-treatment

48 weeks

Every 2 weeks until week 24, then at weeks 32, 40, and 52

What Are the Treatments Tested in This Trial?

Interventions

• Letermovir

Trial Overview The study is testing if Letermovir can prevent cytomegalovirus infection in pediatric patients after a stem cell transplant. The drug aims to stop the virus from multiplying, potentially preventing or lessening the severity of infections.

How Is the Trial Designed?

Group I: ARM I (Letermovir prophylaxis) Experimental Treatment 2 Interventions

Patients receive letermovir PO or IV over 60 minutes QD starting on day +1 post-transplant for 14 weeks. Patients undergo collection of blood samples for CMV PCR analysis weekly for 14 weeks, every 2 weeks until week 24, week 32, week 40 and week 52.

Group II: ARM II (No prophylaxis) Active Control 1 Intervention

Patients undergo collection of blood samples for CMV PCR analysis weekly for 14 weeks, every 2 weeks until week 24, week 32, week 40 and week 52.

Letermovir is already approved in United States, European Union for the following indications:

Approved in United States as Prevymis for:

• Prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT)
• Prophylaxis of cytomegalovirus (CMV) disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-])
• Prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT)
• Prophylaxis of cytomegalovirus (CMV) disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-])

Approved in European Union as Prevymis for:

• Prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT)
• Prophylaxis of cytomegalovirus (CMV) disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-])

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Published Research Related to This Trial

In a 6-year post-marketing surveillance study involving 461 Japanese patients who received allogenic hematopoietic stem-cell transplantation, letermovir was found to be safe, with 13.9% experiencing adverse drug reactions, primarily renal impairment and nausea.

The effectiveness of letermovir for CMV prophylaxis was confirmed, with CMV antigen positivity rates of 21.2% at Week 14 and 37.5% at Week 24 after transplantation, indicating its role in reducing CMV infection risk in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Letermovir in Allogenic Hematopoietic Stem Cell Transplantation Recipients: Interim Report of Post-marketing Surveillance in Japan. Hiraishi, I., Ueno, R., Watanabe, A., et al.[2022]

In a phase 3 trial involving 202 patients with FLT3-ITD acute myeloid leukaemia, sorafenib maintenance post-transplantation significantly reduced the 1-year cumulative incidence of relapse to 7.0% compared to 24.5% in the control group, indicating its efficacy in preventing relapse after allogeneic stem-cell transplantation.

The treatment was well tolerated, with no treatment-related deaths reported, and the most common adverse events were similar between the sorafenib and control groups, suggesting that sorafenib maintenance is a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Xuan, L., Wang, Y., Huang, F., et al.[2021]

Letermovir (Prevymis™) is an effective prophylactic treatment for preventing cytomegalovirus (CMV) infection and disease in adult patients who are CMV-seropositive and have received an allogeneic hematopoietic stem cell transplant, with approvals in Canada and the USA.

The drug works by inhibiting the CMV DNA terminase complex and has received positive regulatory feedback in Europe, indicating its potential for broader international use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir: First Global Approval. Kim, ES.[2019]

In a retrospective analysis of patients who underwent allogeneic hematopoietic stem cell transplantation, letermovir prophylaxis significantly reduced the incidence of clinically significant CMV infections (30.2% vs. 71.6% in the control group) within 100 days, indicating its efficacy in preventing CMV reactivation.

The study also found that letermovir prophylaxis was associated with lower non-relapse mortality (4.7% vs. 19.8% at day 500), and identified that receiving a transplant from a CMV seronegative donor to a seropositive recipient increased the risk of CMV infection even with letermovir treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation. Mizuno, K., Sakurai, M., Kato, J., et al.[2022]

In a phase III trial, letermovir significantly reduced the rate of clinically significant CMV infection in adult CMV-seropositive patients after hematopoietic stem cell transplantation, demonstrating its efficacy as a prophylactic treatment.

The study found no significant relationship between letermovir exposure and the incidence of adverse events or the timing of CMV infection onset, supporting the current dosing recommendations for the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-Response Analyses of Letermovir Following Oral and Intravenous Administration in Allogeneic Hematopoietic Cell Transplantation Recipients. Prohn, M., Cho, CR., Viberg, A., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37207713/

Effectiveness of letermovir for cytomegalovirus prophylaxis ... This review aimed to evaluate the real-world effectiveness of LET in preventing clinically significant CMV infection (csCMVi) for allo-HCT recipients and ...

2. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf410/8211939

Letermovir Prophylaxis Guided by Cytomegalovirus Cell ... Extending letermovir prophylaxis to 200 days (week 28) effectively reduced the incidence of late-onset cs-CMVi to 3% [4]; however, a rebound in ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1706640

Letermovir Prophylaxis for Cytomegalovirus in ... Letermovir at a dose of 240 mg per day was highly effective in preventing CMV viremia after engraftment in transplant recipients and had little toxicity.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1341321X24003209

Effectiveness of letermovir in preventing cytomegalovirus ... The cumulative incidence of CMV reactivation was significantly lower in patients who received LTV prophylaxis at both day 100 (11.1 % vs. 82.4 %, p < 0.001) and ...

5. journals.asm.org journals.asm.org/doi/10.1128/aac.00420-25

Cytomegalovirus prophylaxis with letermovir in pediatric (birth ... At exposures achieved, letermovir was efficacious and safe in preventing clinically significant CMV infection in pediatric allogeneic HCT ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38142695/

Efficacy and safety of extended duration letermovir ... Extending the duration of letermovir prophylaxis to 200 days following HSCT is efficacious and safe in reducing the incidence of late clinically significant ...

7. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf410/8211939?searchresult=1

Letermovir Prophylaxis Guided by Cytomegalovirus Cell ... Letermovir Prophylaxis Guided by Cytomegalovirus Cell-Mediated Immunity Improves the Outcomes of Allogeneic Hematopoietic Stem Cell Transplant ...

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7330/527996/Real-World-Efficacy-and-Safety-of-Letermovir

Real-World Efficacy and Safety of Letermovir Prophylaxis in ... Letermovir exhibited a superior efficacy and safety profile for CMV prophylaxis in adolescent patients undergoing aHCT, as compared to valganciclovir.

9. astctjournal.org astctjournal.org/article/S2666-6367(25)01205-9/fulltext

Letermovir Primary and Secondary Prophylaxis in Pediatric ... Letermovir cuts 3-month CMV reactivation in children from 29.5% to 3.7%. No CMV reactivation observed in high-risk patients on secondary prophylaxis.

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302623003447

Articles Efficacy and safety of extended duration letermovir ... The results of a large, global, phase 3 study (the P001 study) showed that letermovir was well tolerated and superior to placebo in reducing the incidence of ...