Dried Blood Spot Testing of CMV Detection in HCT Recipients

A Multi-Site, Randomized Trial of Subject-Collected Dried Blood Spot CMV Testing With Mobile Technology Support to Optimize Preemptive Therapy Late After Allogeneic HCT

This is a randomized clinical trial to assess whether a subject centered, self-collection of Dried blood spots (DBS) samples will improve compliance with the clinical recommendation of weekly Cytomegalovirus (CMV) testing of Hematopoietic cell transplantation (HCT) recipients who are at high risk for late CMV disease. In this study, mobile devices will be used to remind HCT survivors to perform CMV monitoring using finger-stick collected DBS testing in their home setting or to visit their doctor's office to perform the test. 150 allogeneic HCT recipients > /= 15 years of age will be randomized (2:1) to DBS monitoring or standard of care (per local institution) monitoring. Duration of study participation is anticipated to be within a range of 26 weeks to 43 weeks. The primary objective is to evaluate adherence to recommended CMV monitoring duration and interval during the first year after HCT upon enrollment using subject collected dried blood spot testing.

Study Overview

• Status: Active, not recruiting
• Conditions: Cytomegalovirus Infection
• Intervention / Treatment: Device: DBS Self-Collection Kit; Other: Standard Control Strategy

Detailed Description

This is a randomized clinical trial to assess whether a subject centered, self-collection of Dried blood spots (DBS) samples will improve compliance with the clinical recommendation of weekly Cytomegalovirus (CMV) testing of Hematopoietic cell transplantation (HCT) recipients who are at high risk for late CMV disease. In this study, mobile devices will be used to remind HCT survivors to perform CMV monitoring using finger-stick collected DBS testing in their home setting or to visit their doctor's office to perform the test. 150 allogeneic HCT recipients > /= 15 years of age will be randomized (2:1) to DBS monitoring or standard of care (per local institution) monitoring. Duration of study participation is anticipated to be within a range of 26 weeks to 43 weeks. The primary objective is to evaluate adherence to recommended CMV monitoring duration and interval during the first year after HCT upon enrollment using subject collected dried blood spot testing. The secondary objectives are 1) To evaluate the mean difference between the recommended monitoring that each subject completes between the DBS and the control arm. 2) To compare the incidence of CMV disease between the DBS monitoring and standard of care arm; 3) To evaluate the safety of DBS monitoring.

• Study Type: Interventional
• Enrollment (Actual): 622
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Boeckh; Phone Number: 12066674898; Email: mboeckh@fhcrc.org

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455-0356
      • University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine
  • New York
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030-4000
      • The University of Texas - MD Anderson Cancer Center - Infectious Diseases
  • Washington
    • Seattle, Washington, United States, 98109-4433
      • Fred Hutchinson Cancer Research Center - Vaccine and Infectious Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Randomized Cohort:

1. Must be >/= 15 years of age at the time of enrollment
2. Must be able to provide written consent and complete the informed consent
3. Must have received allogeneic hematopoietic cell transplantation within 60-180 days prior to randomization
4. Cytomegalovirus (CMV) seropositive or had a donor who was CMV positive

5. One or both of the following:

   • CMV event* within the first 100 days post-transplant requiring anti-viral treatment
   • Receipt of CMV prophylaxis**(for at least 30 days) prior to randomization. Continuation of letermovir prophylaxis after day 100 per institutional standard of care is permitted * CMV event defined as deoxyribonucleic acid (DNA) detection or disease ** Anti-viral treatment or prophylaxis includes ganciclovir, valganciclovir, foscarnet, or letermovir
6. Direct availability to the internet either by a computer in the residence or a smart phone

7. Had at least one or more of these conditions:

   • HLA mismatch*
   • umbilical cord blood source**
   • Graft versus host disease (GVHD)***

   • T-cell depletion**** * Human leukocyte antigen (HLA)-related (sibling) donor with at least one mismatch at one of the following three HLA-gene loci: HLA-A, -B, or -DR, Haploidentical donor, Unrelated donor with at least one mismatch at one of the following four HLA-gene loci: HLA-A, -B, -C and -DRB1

     • Use of umbilical cord blood as stem cell source ***Acute or chronic GVHD requiring topical steroid for gastrointestinal (GI) GVHD and/or systemic steroid treatment (>/= 1 mg/kg/day of prednisone or equivalent dose of another corticosteroid) within 6 weeks prior to enrollment

       • Subjects who have received partial or full T-cell depletion (with or without GVHD). T-cell depletion can be given as either ex-vivo or in-vivo for GVHD prophylaxis. T-cell depleting agents include, but are not limited to, anti-thymocyte globulin (ATG) and alemtuzumab

Observation Cohort:

1. Must be >/= 15 years of age at the time of enrollment

2. Must have one of the following:

   - Consented for retrospective studies at their transplant center, or

   - Be included under the auspices of the site's IRB approved waiver of additional consent for retrospective studies

3. Must have received allogeneic hematopoietic cell transplantation within 360 days prior to enrollment
4. CMV seropositive or had a donor who was CMV positive

5. One or both of the following:

   • CMV event* within the first 100 days post-transplant requiring anti-viral treatment
   • Receipt of CMV prophylaxis**(for at least 30 days) prior to registration. Continuation of letermovir prophylaxis after day 100 per institutional standard of care is permitted * CMV event defined as DNA detection or disease ** Anti-viral treatment or prophylaxis includes ganciclovir, valganciclovir, foscarnet, or letermovir

6. Meet at least one or more of criteria of the following:

   • HLA mismatch*
   • umbilical cord blood source**
   • GVHD***

   • T-cell depletion****

     • Human leukocyte antigen (HLA)-related (sibling) donor with at least one mismatch at one of the following three HLA-gene loci: HLA-A, -B, or -DR, Haploidentical donor, Unrelated donor with at least one mismatch at one of the following four HLA-gene loci: HLA-A, -B, -C and -DRB1 **Use of umbilical cord blood as stem cell source ***Acute or chronic GVHD requiring topical steroid for GI GVHD and/or systemic steroid treatment (>/= 1 mg/kg/day of prednisone or equivalent dose of another corticosteroid) within 6 weeks prior to enrollment ****Subjects who have received partial or full T-cell depletion (with or without GVHD). T-cell depletion can be given as either ex-vivo or in-vivo for GVHD prophylaxis. T-cell depleting agents include, but are not limited to, anti-thymocyte globulin (ATG) and alemtuzumab

Exclusion Criteria:

Randomized Cohort:

1. Inability to fully comprehend the study website and study procedures
2. Any other condition, which in the opinion of the investigator would interfere with successful completion of this clinical trial
3. Morphological relapse (bone marrow or peripheral blood blast) prior to registration

Observational Cohort:

1. Did not meet all inclusion criteria
2. Morphological relapse (bone marrow or peripheral blood blast) prior to registration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Self-collected Dried Blood Spot (DBS) monitoring; N=100 Subject collected DBS CMV monitoring with mobile technology support	Device: DBS Self-Collection Kit; Kit for self-collection of Dried Blood Spot (DBS) samples
Active Comparator: Standard Monitoring Control; N=50 Standard care with office based testing	Other: Standard Control Strategy; Standard of care with office-based testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of participants who have completed >90% of their recommended Cytomegalovirus (CMV) monitoring tests in the DBS and control arms	At one year after Hematopoietic cell transplantation (HCT)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects in DBS and standard of care arms with end-organ Cytomegalovirus (CMV) disease, possible and proven/probable	By 1 year after Hematopoietic cell transplantation (HCT)
Number of subjects with finger-stick procedure-related Grade 3 AEs	By 1 year after Hematopoietic cell transplantation (HCT)
The total number of recommended Cytomegalovirus (CMV) monitoring tests that were completed per subject	By 1 year after Hematopoietic cell transplantation (HCT)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2019
• Primary Completion (Estimated): April 25, 2024
• Study Completion (Estimated): August 25, 2024

Study Registration Dates

• First Submitted: April 9, 2019
• First Submitted That Met QC Criteria: April 9, 2019
• First Posted (Actual): April 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Allogeneic; Cytomegalovirus; Hematopoietic cell transplantation; Dried Blood Spot
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: 16-0098; HHSN272201600015C

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No