Clinical trial NCT03910478: Dried Blood Spot Testing of CMV Detection in HCT Recipients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cytomegalovirus Infection
Keywords: Allogeneic
Cytomegalovirus
Dried Blood Spot
Hematopoietic cell transplantation
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2019-04-10
Enrollment: 622
Sex: ALL
Minimum age (years): 15
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Additionally, an observational cohort of 450 HCT recipients, who consented for retrospective studies and meet eligibility criteria but are not participating in the DBS testing for CMV, will be used to assess whether randomized study sample is representative of the DBS study population and to obtain a population-based estimate of late CMV disease.

Eligibility criteria: 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 or acyclovir/valacyclovir (high and low dose) 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, letermovir, maribavir or acyclovir/valacyclovir (high and low dose)
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 during or within 1 year prior to the conduct of the randomized trial (defined as time during which randomization is done)
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 or acyclovir/valacyclovir (high and low dose) 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, letermovir, maribavir or acyclovir/valacyclovir (high and low dose)
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

Primary outcomes:
measure: The Number of Participants Who Have Completed >90% of Their Recommended Cytomegalovirus (CMV) Monitoring Tests in the DBS and Control Arms in the ITT Population
timeFrame: At one year after Hematopoietic cell transplantation (HCT)
measure: The Number of Participants Who Have Completed >90% of Their Recommended Cytomegalovirus (CMV) Monitoring Tests in the DBS and Control Arms in the mITT Population
timeFrame: At one year after Hematopoietic cell transplantation (HCT)
Secondary outcomes:
measure: The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the ITT Population
timeFrame: By 1 year after Hematopoietic cell transplantation (HCT)
measure: The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the mITT Population
timeFrame: By 1 year after Hematopoietic cell transplantation (HCT)
measure: Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable
timeFrame: By 1 year after Hematopoietic cell transplantation (HCT)
measure: Number of Participants With Finger-stick Procedure-related Grade 3 Adverse Events (AEs) in the DBS Arm
timeFrame: By 1 year after Hematopoietic cell transplantation (HCT)
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: The University of Texas - MD Anderson Cancer Center - Infectious Diseases
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center - Vaccine and Infectious Diseases
state: Washington
Study officials:
References: