Cytomegalovirus Infections Clinical Trial
— CMVbreakOfficial title:
Comparison of Two Strategies for Monitoring HCMV Breakthrough Infections During Letermovir Prophylaxis. A Multicenter, Randomized, Open-label Trial
The goal of this clinical trial is to compare two strategies to monitor human cytomegalovirus (HCMV) infections in transplanted patients receiving letermovir (LTV) as anti-HCMV prophylaxis. HCMV infection after transplantation is diagnosed by detection of HCMV DNA in blood. However, due to the peculiar mechanism of action of LTV, most episodes of HCMV DNA detection are caused by release in the blood stream of non-infectious HCMV DNA. In true episodes of productive infection, HCMV DNA in blood is present inside the virion and therefore is resistant to DNAse digestion. Conversely, when non-infectious free-floating HCMV DNA is released in the bloodstream, it will be degraded after treatment of plasma with DNAse and will not be detectable by real-time PCR assays. Researchers will compare determination of HCMV DNA in blood with or without previous digestion of non-infectious free-floating DNA with DNAse. In patients of the Control group HCMV DNA will be tested without DNAse digestion. If HCMV DNA is positive, patients will stop LTV prophylaxis and receive antiviral therapy with another drug. In patients of the Study group HCMV DNA will be tested after DNAse digestion. Only if HCMV DNA is positive after DNAse digestion, patients will stop LTV prophylaxis and receive antiviral therapy with another drug. The main aim of the study is to demonstrate that, by avoiding inappropriate antiviral therapy during LTV prophylaxis, transplant patients will suffer of lower antiviral-drug-related toxicity. A monitoring strategy able to identify true episodes of HCMV productive infection during LTV prophylaxis will lead to a lower rate of inappropriate antiviral therapy and drug-related toxicity without an increased risk of HCMV disease.
Status | Recruiting |
Enrollment | 140 |
Est. completion date | March 2026 |
Est. primary completion date | June 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Age>18 years. - Allogeneic hematopoietic stem cell transplant. - HCMV IgG seropositivity before transplant - Written informed consent. - LTV prophylaxis administration Exclusion Criteria: - Age <18 years. - Inability to comply with the requirements of the protocol. |
Country | Name | City | State |
---|---|---|---|
Italy | ASST-Ospedale Papa Giovanni XXIII | Bergamo | |
Italy | IRCCS Azienda Ospedaliero-Universitaria di Bologna | Bologna | |
Italy | ASST-Spedali Civili | Brescia | BS |
Italy | ASST Grande Ospedale Metropolitano Niguarda | Milano | |
Italy | Fondazione IRCCS Policlinico San Matteo | Pavia | PV |
Italy | Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" | Reggio Calabria | |
Italy | AOU Policlinico Umberto I | Roma | |
Italy | Policlinico Universitario Agostino Gemelli | Roma |
Lead Sponsor | Collaborator |
---|---|
Foundation IRCCS San Matteo Hospital | Ministero della Salute, Italy |
Italy,
Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD; Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017 Jan 1;64(1):87-91. doi: 10.1093/cid/ciw668. Epub 2016 Sep 28. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | - Proportion of patients with positive HCMV DNAemia developing antiviral drug-related toxicity. | Antiviral drug-related toxicity will be considered as neutrophil impairment or kidney injury. Patients who exit before day 100 for death, underlying disease relapse, or transplant rejection after detection of HCMV-positive DNAemia will be considered as failures and counted along with antiviral drug-related toxicities for the analysis of the primary end-point occurring at least 5 days after start of preemptive antiviral therapy | Day 100 | |
Secondary | Proportion of patients developing HCMV DNAemia during LTV prophylaxis. | Day 100 | ||
Secondary | Proportion of patients developing HCMV disease within day 100 and between day 100 and 360 from transplant (key secondary endpoint) | Day 100 and day 360 | ||
Secondary | Proportion of patients stopping LTV prophylaxis and shifting to GCV/VGCV/FOS therapy. | Day 100 | ||
Secondary | Proportion of patients requiring GCV/VGCV/FOS therapy between day 100 and 360. | Day 360 | ||
Secondary | Proportion of patients with persisting HCMV DNAemia. | Positive DNAemia persisting two weeks after the first positive HCMV DNAemia. | Day 360 | |
Secondary | Proportion of patients developing neutropenia between day 100 and 360. | Day 360 | ||
Secondary | Proportion of patients developing HCMV-specific T-cell response at day 100, 180, and 360. | Day 100, day 180 and day 360 | ||
Secondary | Proportion of patients developing LTV-resistant HCMV strains. | Day 100 | ||
Secondary | Cumulative incidence of acute or chronic GvHD. | Day 100 and day 360 | ||
Secondary | Transplant related mortality (TRM), underlying disease relapse, and 1-year survival. | Day 360 |
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