A Study on Cytomegalovirus (CMV) Infection Outcomes Among Hematopoietic Stem Cell Transplant (HSCT) Participants in Europe and Canada

NCT05571137 | Completed

• 1 other identifier: TAK-620-4004
• Study Type: observational
• Target: 118
• Locations: 7 countries
• Sites: 11

Brief Summary

The main aim of the study is to assess the clinical outcomes of current CMV management across different regions of the world (Europe \[EU\] and Canada \[CAN\]). Data will be collected retrospectively from medical charts. No study medicines will be provided to participants in this study.

Conditions

Cytomegalovirus (CMV)

Outcome Measures

Primary Outcomes (23)

• Time From HSCT Until Start of Asymptomatic and Symptomatic Index Episode

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Symptomatic episode is an episode wherein there is "Tissue invasive/end organ disease" or "CMV syndrome" at any time, and asymptomatic when there is no such observation.

  From HSCT up to start date of the index episode (Up to 7 years 3 months)

• Percentage of Participants who are Asymptomatic and Symptomatic at the Index and Recurrent Episodes

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Recurrent episodes are defined as new CMV infection in a participant with previous evidence of CMV infection. Symptomatic episode is an episode wherein there is "tissue invasive/end organ disease" or "CMV syndrome" at any time, and asymptomatic when there is no such observation.

  Up to 7 years 3 months

• Percentage of Participants With CMV Viremia Clearance as Defined by Site Investigator at the Index and Recurrent Episodes

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV-treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Recurrent episodes is defined as new CMV infection in a participant with previous evidence of CMV infection. CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator.

  Up to 7 years 3 months

• Time From Start of Index Episode to CMV Viremia Clearance as Defined by Site Investigator

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator.

  From start of index episode to CMV viremia clearance (Up to 7 years 3 months)

• Percentage of Participants With CMV Viremia Clearance as Defined by Site Investigator at Week 8 After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator. The assessment will be based on Kaplan-Meier estimate.

  At Week 8 after index date

• Percentage of Participants With CMV Viremia Clearance as Defined by Site Investigator at Week 20 After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator. The assessment will be based on Kaplan-Meier estimate.

  At Week 20 after index date

• Percentage of Participants With CMV Viremia Clearance as Defined by Site Investigator at 1-year After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator. The assessment will be based on Kaplan-Meier estimate.

  At 1-year after index date

• Percentage of Participants With Non-Detectable CMV During the Index Episode Prior to and After the Index Date

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) OR pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all transplant sites.

  Up to 7 years 3 months

• Percentage of Participants With Non-Detectable CMV at Week 8 After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all transplant sites. The assessment will be based on Kaplan-Meier estimate.

  At Week 8 after index date

• Percentage of Participants With Non-Detectable CMV at Week 20 After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all transplant sites. The assessment will be based on Kaplan-Meier estimate.

  At Week 20 after index date

• Percentage of Participants With Non-Detectable CMV at 1-year After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all transplant sites. The assessment will be based on Kaplan-Meier estimate.

  At 1-year after index date

• Time From Treatment Initiation to CMV Viremia Clearance as Defined by Site Investigator at the Index Episode

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator.

  From Treatment Initiation to CMV Viremia Clearance (Up to 7 years 3 months)

• Time From Treatment Initiation Until Evidence of Non-detectable CMV at the Index Episode

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all transplant sites.

  Time from treatment initiation until evidence of non-detectable CMV (Up to 7 years 3 months)

• Time From Start of Index Episode to First Symptomatic CMV Diagnosis

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Symptomatic CMV is defined CMV-related tissue invasive disease or CMV syndrome. Time from start of index episode to first symptomatic CMV diagnosis (tissue invasive disease diagnosis) will be reported.

  From start of index episode to first symptomatic CMV diagnosis (Up to 7 years 3 months)

• Time From Stop Date of the Index Episode to First Recurrent Asymptomatic and Symptomatic CMV Viremia

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Recurrent episodes is defined as new CMV infection in a participant with previous evidence of CMV infection.

  From stop date of the index episode to first recurrent asymptomatic and symptomatic CMV viremia (Up to 7 years 3 months)

• Percentage of Participants With Anti-CMV Treatment-related Myelosuppression and Nephrotoxicity

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Percentage of participants with anti-CMV treatment-related myelosuppression and each type nephrotoxicity overall and during the index episode will be reported.

  Up to 7 years 3 months

• Percentage of Participants With Engraftment From HSCT

  Engraftment is the process by which hematopoietic stem cells (HSC) make their way (homing) to free bone marrow (BM) niches where they can find optimal conditions to survive and proliferate. Percentage of participants with engraftment from HSCT will be reported.

  Up to 7 years 3 months

• Percentage of Participants With Graft Versus Host Disease (GvHD) From HSCT and Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date. Percentage of participants with GvHD (acute, chronic) from HSCT and from the index date will be reported.

  Up to 7 years 3 months

• Percentage of Participants With Graft Failure From HSCT and Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date. Graft failure is defined as a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Percentage of participants with graft failure (primary/secondary) from HSCT and index date will be reported.

  Up to 7 years 3 months

• Percentage of Participants who Died due to any Cause From HSCT and Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date. Percentage of participants who died due to any cause from HSCT and from the index date will be reported.

  Up to 7 years 3 months

• Percentage of Participants who Died due to CMV Infection From HSCT and Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date. Percentage of participants who died due to CMV infection from HSCT and the index date will be reported.

  Up to 7 years 3 months

• Number of Genetic Mutations Conferring Anti-CMV Resistance From HSCT and at Index Episode

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Genetic mutation includes UL27, UL54, UL56, UL97, other, unknown mutation. Number of genetic mutations conferring anti-CMV resistance from HSCT and at index date will be reported.

  Up to 7 years 3 months

• Percentage of Participants With a Genetic Mutation Conferring Anti-CMV Resistance From HSCT and at Index Episode

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Genetic mutation includes UL27, UL54, UL56, UL97, other, unknown mutation. Percentage of participants with a genetic mutation (i.e., UL27, UL54, UL56, UL97, other, unknown) conferring anti-CMV resistance from HSCT and at the index episode will be reported.

  Up to 7 years 3 months

Secondary Outcomes (20)

• Percentage of Participants With Anti-CMV Primary or Secondary Prophylaxis and Pre-emptive Treatment

  Up to 7 years 3 months

• Number of Anti-CMV Therapies Used for Primary or Secondary Prophylaxis and Pre-emptive Treatment

  Up to 7 years 3 months

• Duration of Anti-CMV Prophylaxis Therapy

  Up to 7 years 3 months

• Percentage of Participants With Mono-therapy and Dual-therapy of Anti-CMV Agents of Interest During CMV Episodes

  Up to 7 years 3 months

• Number of Individual and Dual-therapy of Anti-CMV Agents Used During CMV Episodes

  Up to 7 years 3 months

Study Arms (2)

Cohort 1: Resistant, Refractory, or Intolerant (RRI) to Anti-CMV treatment

Participants who had a HSCT after January 1, 2016, and developed post-transplant CMV infection were subsequently characterized as RRI to currently available anti-CMV treatment for at least 12 months before being enrolled, will be observed in this retrospective study for 24 months.

Cohort 2: Pre-emptive CMV Treatment

Participants who had a HSCT after January 1, 2019, were preemptively treated for CMV for at least 12 months before being enrolled, will be observed in this retrospective study for 24 months.

Eligibility Criteria

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

Study Population

Participants who had a CMV infection treated with at least one anti-CMV agent and considered resistant, refractory, or intolerant to a currently available agent will be enrolled in Cohort 1 and participants who received pre-emptive therapy for CMV viremia will be enrolled in Cohort 2.

You may qualify if:

• (Cohort 1) Resistant / Refractory or Intolerant:
• Aged greater than and equal to (\>=) 18 years at the time of the HSCT.
• Received an HSCT after January 1, 2016.
• Diagnosed with CMV infection any time after the HSCT date.
• Required \>=1 anti-CMV agent to manage CMV infection and were subsequently considered:
• resistant to currently available anti-CMV agent; OR
• refractory to currently available anti-CMV agent; OR
• intolerant to currently available anti-CMV agent.
• Follow-up information is available for at least 12 months from the index date (i.e., date when the participant was first considered resistant, refractory or intolerant to anti-CMV agent) or death, whichever occurs first.
• Provided written informed consent prior to the initiation of any study procedures (unless waiver was granted by Institutional Ethical Committee \[IEC\]).
• (Cohort 2) Pre-emptive treatment for CMV viremia:
• Aged \>=18 years at the time of the HSCT.
• Received an HSCT after January 1, 2019.
• Diagnosed with CMV viremia any time after the HSCT date and received pre-emptive anti-CMV agent.
• Follow-up information is available for at least 12 months from the index date (i.e., date when the patient was first preemptively treated with an anti-CMV agent) or death, whichever occurs first.

You may not qualify if:

• Diagnosed as being positive for human immunodeficiency virus before the HSCT.
• Unable to demonstrate a minimum of 12 months of follow-up from the index date (e.g., incomplete information on dates showing follow-up time).
• Participation in a clinical trial related to CMV treatment during the study period.

Sponsors & Collaborators

• Takeda: lead

Study Sites (11)

MU Graz

Graz, 8036, Austria

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Hamilton Health Sciences Corporation

Hamilton, Ontario, L8N 3Z5, Canada

Location

McGill University Health Centre

Montreal, Quebec, H3H 2R9, Canada

Location

Attikon General University Hospital

Athens, 124 62, Greece

Location

George Papanikolau

Thessaloniki, 570 10, Greece

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Institute of Hematology and Transfusion Medicine (IHTM)

Warsaw, 02-776, Poland

Location

University Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Clinical Center of Vojvodina

Novi Sad, 21000, Serbia

Location

Related Links

• To obtain more information on the study, click here/on this link

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 7, 2022
• Study Start: May 31, 2023
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

GR (2); IL (2); PL (1); SE (2); AU (1); BE (1); CA (2)