Letermovir for Preventing CMV Infection After Bone Marrow Transplant

No longer recruiting at 1 trial location

Overseen By Yeon Joo Lee, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Pimozide, Ergot alkaloids, Pitavastatin, Simvastatin

Disqualifiers: Severe hepatic impairment, HIV, HCV, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 100

Duration: 14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if letermovir (Prevymis) can prevent the return of Cytomegalovirus (CMV) infection in individuals who have undergone a bone marrow transplant. It targets those who have previously had CMV and completed specific treatments after their transplant no more than a week ago. Individuals concerned about CMV recurrence after a bone marrow transplant might be suitable candidates. Participants will take letermovir for 14 weeks, with regular blood tests to monitor the virus. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Do I have to stop taking my current medications for the trial?

The trial does not specify that you must stop all current medications, but certain medications are not allowed. You cannot take high doses of acyclovir, valacyclovir, or famciclovir, and some medications like pimozide, ergot alkaloids, and certain statins are not allowed with letermovir. Check with the trial team to see if your current medications are compatible.

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

Research has shown that letermovir is generally safe for individuals who have undergone a bone marrow transplant. One study found that letermovir effectively prevents CMV (Cytomegalovirus) infection and has few harmful side effects. Another review confirmed its safety in preventing CMV reactivation after a transplant. These findings suggest that letermovir is well-tolerated and could be a good option for preventing CMV infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Letermovir is unique because it specifically targets the CMV virus, preventing its reactivation in patients who have undergone bone marrow transplants. Unlike the standard antiviral treatments like ganciclovir or foscarnet, which can have significant side effects like bone marrow suppression, letermovir offers a more tolerable safety profile. Researchers are excited about this treatment because it provides an effective prophylactic option without the common toxicities associated with other antivirals, potentially improving patients' overall quality of life post-transplant.

What evidence suggests that letermovir is effective for preventing CMV infection after a bone marrow transplant?

Research shows that letermovir, which participants in this trial will receive, effectively prevents Cytomegalovirus (CMV) from reactivating after a bone marrow transplant. Studies have found that letermovir significantly reduces the risk of CMV appearing in the blood. Known for its low toxicity, letermovir is safer for long-term use. Real-world data supports its success in preventing serious CMV infections in transplant patients. Overall, letermovir is a promising option for those at risk of CMV reactivation after a transplant. ^{1 2 6 7 8}

Who Is on the Research Team?

Genovefa Papanicolaou, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older who have had a bone marrow transplant, received treatment for CMV infection post-transplant, and are at risk of the infection returning. They must be able to consent (or have a guardian consent), follow trial procedures, and use effective contraception if applicable. People with severe kidney or liver issues, certain drug interactions, HIV/HCV/HBsAg positivity, need for intensive care support, pregnancy/breastfeeding intentions during the trial period cannot join.

Inclusion Criteria

Willing and able to comply with trial instructions and requirements

I've completed treatment for a serious CMV infection within the last 7 days.

I can give my consent, or if under 18, my guardian can and I agree to participate.

Exclusion Criteria

Glomerular filtration rate (GFR) </= mL/min/1.73m^2(equivalent to creatinine clearance </=10 mL/min)

I have received up to two doses of IV cidofovir for ADV.

I use high-dose antiviral medication regularly, but only short treatments for severe infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive letermovir for 14 weeks to prevent recurrent CMV infection

14 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Visits on day 100 and day 180 for blood sample collection

What Are the Treatments Tested in This Trial?

Interventions

• Letermovir

Trial Overview

The study tests whether Letermovir pills can prevent the recurrence of Cytomegalovirus (CMV) infection in patients who've previously been treated for CMV after receiving a bone marrow transplant. Participants will take Letermovir and undergo regular blood draws to monitor their health.

How Is the Trial Designed?

Group I: Hematopoietic cell transplantation/HCT Experimental Treatment 2 Interventions

Participants will be hematopoietic cell transplantation (HCT) recipients with a history of CMV infection. INTERVENTIONAL COHORT: Patients receive letermovir PO QD (or IV over 1 hour for patients unable to receive PO) for 14 weeks in the absence of disease progression or unacceptable toxicity. OBSERVATIONAL COHORT: Patients undergo collection of blood samples for CMV-CMI analysis via CMV immunity T cell panel assay on day 100. Patients with negative CMI on day 100 undergo collection of blood samples for retesting on day 180.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10781138/

Efficacy and safety of letermovir prophylaxis for ...

Several studies have reported that letermovir can effectively prevent CMV activation after allogeneic hematopoietic stem cell transplantation ( ...

2.

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.

3.

academic.oup.com

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

Letermovir Prophylaxis Guided by Cytomegalovirus Cell ...

This study aimed to assess whether CMV-CMI–guided letermovir prophylaxis is more effective than a fixed-duration approach in reducing the ...

4.

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 ...

5.

sciencedirect.com

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

Effectiveness of letermovir in preventing cytomegalovirus ...

Letermovir (LTV), a CMV terminase inhibitor, has been reported to prevent clinically significant CMV infection with low toxicity in a randomized phase 3 trial ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02137772

NCT02137772 | Letermovir (MK-8228) Versus Placebo in ...

The hypothesis being tested was that MK-8228 is superior to placebo in the prevention of clinically-significant CMV infection through Week 24 post-transplant.

7.

sciencedirect.com

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

Articles 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 ...

8.

astctjournal.org

astctjournal.org/article/S1083-8791(20)30663-7/fulltext

Letermovir for Prevention of Cytomegalovirus Reactivation ...

In summary, letermovir was effective in preventing CMV infection in this high-risk population of HLA-mismatched allo-HCT recipients. Key Words. Haploidentiacl ...