Dried Blood Spot Testing of CMV Detection in HCT Recipients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cytomegalovirus Infection

Intervention / Treatment
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* Device: DBS Self-Collection Kit
* Other: Standard Control Strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Randomized Cohort: Must be >/= 15 years of age at the time of enrollment Must be able to provide written consent and complete the informed consent Must have received allogeneic hematopoietic cell transplantation within 60-180 days prior to randomization Cytomegalovirus (CMV) seropositive or had a donor who was CMV positive 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 Direct availability to the internet either by a computer in the residence or a smart phone 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: Must be >/= 15 years of age at the time of enrollment 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 Must have received allogeneic hematopoietic cell transplantation within 360 days prior to enrollment CMV seropositive or had a donor who was CMV positive 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 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: Inability to fully comprehend the study website and study procedures Any other condition, which in the opinion of the investigator would interfere with successful completion of this clinical trial Morphological relapse (bone marrow or peripheral blood blast) prior to registration Observational Cohort: Did not meet all inclusion criteria Morphological relapse (bone marrow or peripheral blood blast) prior to registration

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic, Cytomegalovirus, Dried Blood Spot, Hematopoietic cell transplantation