Letermovir (LMV) prophylaxis in CMV-seronegative Allogeneic Stem Cell Transplant Recipients with CMV seropositive donors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Grupo Espanol De Trasplante Hematopoyetico Y Terapia Celular

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

13 Nov 2024 → ongoing

Decision date (initial)

2024-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To determinate the incidence of csCMV infection through week 14 post-SCT.

Secondary objectives 15

1. To determinate the incidence of csCMV infection through week 14 post-SCT.
2. Describe the patient profile breakthrough CMV DNAemia
3. Engraftment incidence and time to engraftment
4. All-cause mortality by week 14 and day 180
5. Non-relapse Mortality (NRM) by week 14 and day 180
6. To evaluate the time to onset of all-cause failure of prophylaxis against CMV infection during the 14 weeks of study-drug administration period
7. To estimate the duration of CMV-antiviral treatments by day 180 post-SCT.
8. To determinate the direct costs of CMV-antiviral treatments and hospital resource utilization by day 180 post-SCT.
9. To investigate the natural history of blips in the LMV primary prophylaxis (PP) clinical setting
10. Incidence of low levels of CMV DNAemia not requiring PET
11. To evaluate LMV tolerance and safety
12. To evaluate de incidence of aGVHD and clinical characteristics.
13. To evaluate de incidence of relapse and clinical characteristics.
14. To establish incidence of late (> d +100) clinically significant CMV DNAemia
15. To establish de incidence of non-CMV infections.

Conditions and MedDRA coding

Cytomegalovirus infection in allogeneic stem cell transplant recipients

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥18 years
2. First allogenic HCT.
3. Pre-HCT patient CMV negative IgG serology with CMV IgG positive donor serostatus.
4. Able to provide written consent and complete the informed consent.
5. Absence of CMV DNAemia requiring antiviral therapy within 5 days before initiation of LMV.

Exclusion criteria 10

1. Active pre-emptive therapy for csCMV-I.
2. Patients who have received LMV prophylaxis prior to enrollment.
3. Glomerular filtration rate (GFR) </=30 mL/min/1.73m^2 (equivalent to creatinine clearance (ClCr) </=10 mL/min).
4. Severe hepatic function grade 3-4 CTAE at the time of study entry.
5. Suspected or known hypersensitivity to active or inactive ingredients of LMV formulations.
6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to LMV
7. Patients with previous untreated reactivation.
8. Pregnancy or breastfeeding.
9. Plans to conceive or father children within the projected duration of the trial.
10. History of current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or would place the subject at undue risk as judged by the investigator, such that it is not in the best interest of the subject to participate in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. csCMV infection is considered in case the patient requires pharmacological treatment according to standard clinical practice.

Secondary endpoints 15

1. csCMV infection is considered in case the patient requires pharmacological treatment according to standard clinical practice.
2. Clinical characteristic
3. Neutrophile (>0,5x10e9/L) and platelets engraftment (>20 x10e9/L) by week 4 and week 14
4. Death by any cause and death not related with disease relapse or progression
5. Death by any cause non related to relapse by week 14 and day 180
6. Time to onset of all-cause failure of prophylaxis against CMV infection during the 14 weeks of study-drug administration period including patients who discontinued the study drug because of virologic failure or for any other reason (e.g., an adverse event, nonadherence, or consent withdrawal).
7. Duration of any CMV-antiviral treatment by day 180 post-SCT
8. Direct cost of CMV-antiviral treatment and hospital resource
9. Incidence of blips, clinical and analytic characteristics.
10. Incidence of untreated CMV DNAemia
11. Adverse events according to the CTCAE, physical examination and regular laboratory tests. Only adverse events (AE) related to the treatment according to investigator
12. Incidence of aGVHD within 120 days after HCT and its onset and severity
13. Incidence of relapse within 180 days after HCT and its onset and severity
14. Incidence of CMV DNAemia requiring PET within 100-180 days after HCT
15. Incidence of non-CMV infections within 180 days after HCT and its onset and severity

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Grupo Espanol De Trasplante Hematopoyetico Y Terapia Celular

Sponsor organisation

Grupo Espanol De Trasplante Hematopoyetico Y Terapia Celular

Address

Calle Aravaca 12 1 B, Poligono Los Vascos Poligono Los Vascos

City

Madrid

Postcode

28040

Country

Spain

Scientific contact point

Organisation

Grupo Español de Trasplantes Hematopoyéticos y Terapia Celular

Contact name

Sponsor

Public contact point

Organisation

Grupo Español de Trasplantes Hematopoyéticos y Terapia Celular

Contact name

Sponsor

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications