Cytomegalovirus Infection
Conditions
Keywords
Allogeneic, Cytomegalovirus, Dried Blood Spot, Hematopoietic cell transplantation
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.
Interventions
Standard of care with office-based testing.
DEVICEDBS Self-Collection Kit
Kit for self-collection of Dried Blood Spot (DBS) samples
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | At one year after Hematopoietic cell transplantation (HCT) | To evaluate adherence to recommended CMV monitoring duration and interval during the first year after HCT, the number of participants who completed \>90% of their recommended CMV monitoring tests at one year after HCT in the DBS and control arms was collected. |
| 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 | At one year after Hematopoietic cell transplantation (HCT) | To evaluate adherence to recommended CMV monitoring duration and interval during the first year after HCT, the number of participants who completed \>90% of their recommended CMV monitoring tests at one year after HCT in the DBS and control arms was collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the ITT Population | By 1 year after Hematopoietic cell transplantation (HCT) | The total number of recommended Cytomegalovirus (CMV) monitoring tests that were completed per participant was reported. |
| The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the mITT Population | By 1 year after Hematopoietic cell transplantation (HCT) | The total number of recommended Cytomegalovirus (CMV) monitoring tests that were completed per participant was reported. |
| Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | By 1 year after Hematopoietic cell transplantation (HCT) | Proven or probable CMV disease is a serious adverse event of special interest. The number of participants experiencing proven or probable CMV disease between Hematopoietic cell transplantation (HCT) and 365 days after HCT. |
| Number of Participants With Finger-stick Procedure-related Grade 3 Adverse Events (AEs) in the DBS Arm | By 1 year after Hematopoietic cell transplantation (HCT) | To evaluate the safety of DBS monitoring, Finger-stick procedure-related Grade 3 AEs were abstracted through medical chart review at quarterly contacts and at the final close-out contact. Participants were considered as meeting the outcome measure if they had at least one finger-stick procedure-related Grade 3 AE during the study period. |
Countries
United States
Participant flow
Recruitment details
Participants who were considered by their transplant teams to be at risk for late CMV disease and were clinically recommended to continue CMV monitoring after day 100 post-transplant were recruited from 4 clinical sites within the United States. The first participant was enrolled on May 3, 2019 and the last participant was enrolled on July 27, 2023.
Participants by arm
| Arm | Count |
|---|---|
| Self-collected Dried Blood Spot (DBS) Monitoring Participants collected DBS CMV monitoring with mobile technology support.
DBS Self-Collection Kit: Kit for self-collection of Dried Blood Spot (DBS) samples. | 113 |
| Standard Monitoring Control Standard care with office based testing.
Standard Control Strategy: Standard of care with office-based testing. | 59 |
| Total | 172 |
Baseline characteristics
| Characteristic | Self-collected Dried Blood Spot (DBS) Monitoring | Standard Monitoring Control | Total |
|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 14.4 | 49.7 years STANDARD_DEVIATION 16 | 52.2 years STANDARD_DEVIATION 15 |
| Days from HCT | 88.6 days STANDARD_DEVIATION 24.4 | 86.2 days STANDARD_DEVIATION 15.4 | 87.8 days STANDARD_DEVIATION 21.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 10 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants | 48 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Perceived Ease of Access to Blood Draw Facility Difficult | 16 Participants | 8 Participants | 24 Participants |
| Perceived Ease of Access to Blood Draw Facility Easy | 97 Participants | 51 Participants | 148 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) White | 83 Participants | 42 Participants | 125 Participants |
| Sex: Female, Male Female | 39 Participants | 30 Participants | 69 Participants |
| Sex: Female, Male Male | 74 Participants | 29 Participants | 103 Participants |
| Transplant Site Fred Hutchinson Cancer Research Center | 34 Participants | 18 Participants | 52 Participants |
| Transplant Site MD Anderson Cancer Center | 38 Participants | 20 Participants | 58 Participants |
| Transplant Site Memorial Sloan Kettering Cancer Center | 19 Participants | 8 Participants | 27 Participants |
| Transplant Site University of Minnesota Medical School | 22 Participants | 13 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 113 | 7 / 59 |
| other Total, other adverse events | 0 / 94 | 0 / 0 |
| serious Total, serious adverse events | 2 / 94 | 2 / 58 |
Outcome results
Primary
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
To evaluate adherence to recommended CMV monitoring duration and interval during the first year after HCT, the number of participants who completed \>90% of their recommended CMV monitoring tests at one year after HCT in the DBS and control arms was collected.
Time frame: At one year after Hematopoietic cell transplantation (HCT)
Population: The Intention-to-Treat population (ITT) included all participants in the randomized cohort in the intervention group to which they were randomly assigned, regardless of their monitoring compliance and regardless of subsequent withdrawal or deviation from the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Self-collected Dried Blood Spot (DBS) Monitoring | 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 | 27 Participants |
| Standard Monitoring Control | 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 | 15 Participants |
Comparison: A traditional logistic regression model was fit where the outcome was whether or not participants completed \> 90% of their clinician-recommended CMV monitoring tests in the study period by 1-year after HCT.p-value: 0.89295% CI: [0.438, 2.053]Regression, Logistic
Primary
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
To evaluate adherence to recommended CMV monitoring duration and interval during the first year after HCT, the number of participants who completed \>90% of their recommended CMV monitoring tests at one year after HCT in the DBS and control arms was collected.
Time frame: At one year after Hematopoietic cell transplantation (HCT)
Population: The mITT population included all participants in the ITT population who had at least one result for the number of clinician-recommended CMV monitoring tests and remained enrolled through their first scheduled clinician recommended CMV monitoring test. Participants were grouped based on the intervention received, where participants that completed at least one self-collected DBS sample were grouped in the DBS arm and all other participants were grouped in the SOC arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Self-collected Dried Blood Spot (DBS) Monitoring | 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 | 22 Participants |
| Standard Monitoring Control | 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 | 20 Participants |
Comparison: A traditional logistic regression model was fit where the outcome was whether or not participants completed \> 90% of their clinician -recommended CMV monitoring tests in the study period by 1-year after HCT.p-value: 0.300895% CI: [0.301, 1.45]Regression, Logistic
Secondary
Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable
Proven or probable CMV disease is a serious adverse event of special interest. The number of participants experiencing proven or probable CMV disease between Hematopoietic cell transplantation (HCT) and 365 days after HCT.
Time frame: By 1 year after Hematopoietic cell transplantation (HCT)
Population: The Intention-to-Treat population (ITT) included all participants in the randomized cohort in the intervention group to which they were randomly assigned, regardless of their monitoring compliance and regardless of subsequent withdrawal or deviation from the protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Self-collected Dried Blood Spot (DBS) Monitoring | Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | Possible | 0 Participants |
| Self-collected Dried Blood Spot (DBS) Monitoring | Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | Probable | 0 Participants |
| Self-collected Dried Blood Spot (DBS) Monitoring | Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | Proven | 2 Participants |
| Self-collected Dried Blood Spot (DBS) Monitoring | Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | Probable/Proven | 2 Participants |
| Standard Monitoring Control | Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | Probable/Proven | 2 Participants |
| Standard Monitoring Control | Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | Possible | 0 Participants |
| Standard Monitoring Control | Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | Proven | 2 Participants |
| Standard Monitoring Control | Number of Participants With End-organ Cytomegalovirus (CMV) Disease, Possible and Proven/Probable | Probable | 0 Participants |
Secondary
Number of Participants With Finger-stick Procedure-related Grade 3 Adverse Events (AEs) in the DBS Arm
To evaluate the safety of DBS monitoring, Finger-stick procedure-related Grade 3 AEs were abstracted through medical chart review at quarterly contacts and at the final close-out contact. Participants were considered as meeting the outcome measure if they had at least one finger-stick procedure-related Grade 3 AE during the study period.
Time frame: By 1 year after Hematopoietic cell transplantation (HCT)
Population: The safety population consist of all enrolled participants that had any safety data collected after randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Self-collected Dried Blood Spot (DBS) Monitoring | Number of Participants With Finger-stick Procedure-related Grade 3 Adverse Events (AEs) in the DBS Arm | 0 Participants |
Secondary
The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the ITT Population
The total number of recommended Cytomegalovirus (CMV) monitoring tests that were completed per participant was reported.
Time frame: By 1 year after Hematopoietic cell transplantation (HCT)
Population: The Intention-to-Treat population (ITT) included all participants in the randomized cohort in the intervention group to which they were randomly assigned, regardless of their monitoring compliance and regardless of subsequent withdrawal or deviation from the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Self-collected Dried Blood Spot (DBS) Monitoring | The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the ITT Population | 6 number of monitoring tests completed |
| Standard Monitoring Control | The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the ITT Population | 11 number of monitoring tests completed |
Secondary
The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the mITT Population
The total number of recommended Cytomegalovirus (CMV) monitoring tests that were completed per participant was reported.
Time frame: By 1 year after Hematopoietic cell transplantation (HCT)
Population: The mITT population included all participants in the ITT population who had at least one result for the number of clinician-recommended CMV monitoring tests and remained enrolled through their first scheduled clinician recommended CMV monitoring test. Participants were grouped based on the intervention received, where participants that completed at least one self-collected DBS sample were grouped in the DBS arm and all other participants were grouped in the SOC arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Self-collected Dried Blood Spot (DBS) Monitoring | The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the mITT Population | 11 number of monitoring tests completed |
| Standard Monitoring Control | The Total Number of Recommended Cytomegalovirus (CMV) Monitoring Tests That Were Completed Per Participant in the mITT Population | 11 number of monitoring tests completed |