Letermovir Prophylaxis for CMV Infection in Haplo-HSCT Recipients: Single-center Data in China

NCT05789615 | Completed DMC

• 1 other identifier: SOOCHOW-WXJ-2022-366
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

In the 30 years of fighting CMV infection, the mortality rate among HSCT patients has significantly reduced. Now, the focus is on improving the prognosis of HSCT patients and preventing CMV infection. The emergence of letermovir has provided a new opportunity in this regard. Letermovir, the only drug approved for CMV infection prevention in HSCT patients, works by inhibiting the CMV DNA terminase complex. Phase III studies have shown that letermovir significantly reduces CMV infection and all-cause mortality after HSCT, without increasing myelosuppression or nephrotoxicity. Real-world studies have further confirmed its efficacy in reducing CMV infection rates and antiviral use. Letermovir's global success has not yet been fully realized in China, where it is still in its early stages of use.

Conditions

CMV Infection; Hematopoietic Stem Cell Transplantation

Keywords

Letermovir; Cytomegalovirus Infection; Haploidentical HSCT

Outcome Measures

Primary Outcomes (1)

• Incidence of clinically significant CMV infection

  Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease using classificatory criteria published by the Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. CMV DNA threshold for initiation of preemptive therapy at our center is viral load \>500 copies/mL or above on two consecutive tests.

  at Week 14 following haplo-SCT

Secondary Outcomes (8)

• Incidence of clinically significant CMV infection

  through Week 24 following haplo-SCT

• Incidence of CMV DNAemia and CMV disease

  through Week 14 and Week 24 following haplo-SCT

• Incidence of the resistant or refractory CMV infection

  through Week 24 following haplo-SCT

• Incidence of serious adverse event leading to interruption of treatment

  through Week 24 following haplo-SCT

• Incidence of CMV-related disease mortality

  through Week 24 following haplo-SCT

Study Arms (1)

200 haplo-HSCT recipients who are CMV seropositive

The study consists 200 cases CMV-R+ adult (\>18 years) recipients of haplo-HCT. All patients will receive letermovir prophylaxis. Consider a simple interim analysis of the experimental group could be arranged after 150 patients are enrolled if necessary. Supportive care is provided by institutional standards of care (e.g., acyclovir for herpes simplex virus and varicella zoster virus prevention). Letermovir prophylaxis is started on day 0 or no longer than 28 days after transplantation. During the study period, letermovir 480 mg PO/IV once daily (or 240 mg per day in patients taking cyclosporine) was administered from day 0 to day +100 post-HCT. CMV monitoring and preemptive therapy were performed according to local protocol. Plasma CMV viral load (VL) is monitored by quantitative CMV PCR, starting on day +7 and continued weekly until week 6, then every 2-4 weeks for months until week 24.

Drug: Letermovir

Interventions

Letermovir DRUG

Letermovir has achieved excellent therapeutic benefits globally but is still in its infancy in China. Letermovir obtained an implied license for a clinical trial in June 2020, and in November 2020, Letermovir submitted and accepted four new drug marketing applications in China, including injection and tablet formulations. On December 31, 2021, the China National Medical Products Administration (NMPA) approved letermovir for cytomegalovirus (CMV) seropositive adult recipients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) \[R+\] prevention of cytomegalovirus infection and cytomegalovirus disease. The commercial launch of letermovir is estimated to be in August 2022.

200 haplo-HSCT recipients who are CMV seropositive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study consists 200 cases CMV-R+ adult (\>18 years) recipients of haplo-HCT. All patients will receive letermovir prophylaxis.

You may qualify if:

• Haplo-SCT candidate (adult) who has decided to primary transplant and is willing to participate in the study.
• The haplo-SCT candidate (adult) should be CMV seropositive recipients.

You may not qualify if:

• CMV-seronegative patient receiving a negative CMV donor graft.
• Patients having active CMV DNAemia at the time of letermovir initiation.
• Patient having signed the informed consent but not grafted.
• Patient recruited in a clinical study on an anti-CMV trial.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The First Affiliated Hospital of Soochow university

Suzhou, Jiangsu, China

Location

Related Publications (12)

• Styczynski J. Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation. Infect Dis Ther. 2018 Mar;7(1):1-16. doi: 10.1007/s40121-017-0180-z. Epub 2017 Dec 4.

  PMID: 29204910 BACKGROUND

• Green ML, Leisenring W, Xie H, Mast TC, Cui Y, Sandmaier BM, Sorror ML, Goyal S, Ozkok S, Yi J, Sahoo F, Kimball LE, Jerome KR, Marks MA, Boeckh M. Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016 Mar;3(3):e119-27. doi: 10.1016/S2352-3026(15)00289-6. Epub 2016 Feb 20.

  PMID: 26947200 BACKGROUND

• Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ; Center for International Blood and Marrow Research; National Marrow Donor program; European Blood and MarrowTransplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow Transplant Group; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America; Association of Medical Microbiology and Infectious Disease Canada; Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009 Oct;15(10):1143-238. doi: 10.1016/j.bbmt.2009.06.019. No abstract available.

  PMID: 19747629 BACKGROUND

• Akahoshi Y, Kimura SI, Inamoto Y, Seo S, Muranushi H, Shimizu H, Ozawa Y, Tanaka M, Uchida N, Kanda Y, Katayama Y, Shiratori S, Ota S, Matsuoka KI, Onizuka M, Fukuda T, Atsuta Y, Murata M, Terakura S, Nakasone H. Effect of Cytomegalovirus Reactivation With or Without Acute Graft-Versus-Host Disease on the Risk of Nonrelapse Mortality. Clin Infect Dis. 2021 Aug 2;73(3):e620-e628. doi: 10.1093/cid/ciaa1871.

  PMID: 33341890 BACKGROUND

• Hakki M, Aitken SL, Danziger-Isakov L, Michaels MG, Carpenter PA, Chemaly RF, Papanicolaou GA, Boeckh M, Marty FM. American Society for Transplantation and Cellular Therapy Series: #3-Prevention of Cytomegalovirus Infection and Disease After Hematopoietic Cell Transplantation. Transplant Cell Ther. 2021 Sep;27(9):707-719. doi: 10.1016/j.jtct.2021.05.001.

  PMID: 34452721 BACKGROUND

• Razonable R. Direct and indirect effects of cytomegalovirus: can we prevent them? Enferm Infecc Microbiol Clin. 2010 Jan;28(1):1-5. doi: 10.1016/j.eimc.2009.07.008. Epub 2009 Dec 21. No abstract available.

  PMID: 20022410 BACKGROUND

• Goodrich JM, Mori M, Gleaves CA, Du Mond C, Cays M, Ebeling DF, Buhles WC, DeArmond B, Meyers JD. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med. 1991 Dec 5;325(23):1601-7. doi: 10.1056/NEJM199112053252303.

  PMID: 1658652 BACKGROUND

• Boeckh M, Nichols WG. The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood. 2004 Mar 15;103(6):2003-8. doi: 10.1182/blood-2003-10-3616. Epub 2003 Nov 26.

  PMID: 14644993 BACKGROUND

• Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, Haider S, Ullmann AJ, Katayama Y, Brown J, Mullane KM, Boeckh M, Blumberg EA, Einsele H, Snydman DR, Kanda Y, DiNubile MJ, Teal VL, Wan H, Murata Y, Kartsonis NA, Leavitt RY, Badshah C. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017 Dec 21;377(25):2433-2444. doi: 10.1056/NEJMoa1706640. Epub 2017 Dec 6.

  PMID: 29211658 BACKGROUND

• Su Y, Stern A, Karantoni E, Nawar T, Han G, Zavras P, Dumke H, Cho C, Tamari R, Shaffer B, Giralt S, Jakubowski A, Perales MA, Papanicolaou G. Impact of Letermovir Primary Cytomegalovirus Prophylaxis on 1-Year Mortality After Allogeneic Hematopoietic Cell Transplantation: A Retrospective Cohort Study. Clin Infect Dis. 2022 Sep 14;75(5):795-804. doi: 10.1093/cid/ciab1064.

  PMID: 34979021 BACKGROUND

• Derigs P, Radujkovic A, Schubert ML, Schnitzler P, Schoning T, Muller-Tidow C, Hegenbart U, Schonland SO, Luft T, Dreger P, Schmitt M. Letermovir prophylaxis is effective in preventing cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: single-center real-world data. Ann Hematol. 2021 Aug;100(8):2087-2093. doi: 10.1007/s00277-020-04362-2. Epub 2020 Dec 3.

  PMID: 33270162 BACKGROUND

• Sassine J, Khawaja F, Shigle TL, Handy V, Foolad F, Aitken SL, Jiang Y, Champlin R, Shpall E, Rezvani K, Ariza-Heredia EJ, Chemaly RF. Refractory and Resistant Cytomegalovirus After Hematopoietic Cell Transplant in the Letermovir Primary Prophylaxis Era. Clin Infect Dis. 2021 Oct 20;73(8):1346-1354. doi: 10.1093/cid/ciab298.

  PMID: 33830182 BACKGROUND

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

letermovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Xiaojin Wu, Prof.

  The First Affiliated Hospital of Soochow University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: March 29, 2023
• Study Start: April 1, 2023
• Primary Completion: January 10, 2025
• Study Completion: January 10, 2025
• Last Updated: February 19, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)