Allogeneic Stem Cell Transplantation, CMV
Conditions
Keywords
CMV T Cell Immunity Panel, CMV reactivation, Allogeneic stem cell transplantation, Letermovir
Brief summary
This is a phase 2, prospective cohort clinical trial evaluating the utilization of CMV T Cell Immunity Panel (CMV-TCIP) assay to guide the duration of primary CMV prophylaxis in CMV-seropositive recipients of allogeneic stem cell transplant or recipients receiving a stem cell graft from a CMV serology positive donor.
Interventions
DRUGLetermovir
Subjects will receive 14 weeks of letermovir prophylaxis at standard recommended dose follow by CMV-TCIP-directed extended prophylaxis.
DEVICECMV T Cell Immunity Panel (CMV-TCIP)
Viracor CMV-TCIP assay to measure how a person's immune system responds to CMV. Viracor CMV-TCIP will be measured monthly, starting at week 14, until positive, then at week 30 and 52.
DIAGNOSTIC_TESTCMV DNA PCR
Plasma level of CMV DNA PCR will be measured at enrollment and at least weekly through week 30, then at least every 2 weeks through week 52 of transplant if no GVHD or CMV reactivation.
Sponsors
University of California, Irvine
Eurofins Viracor
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age on the day of signing informed consent. * Karnofsky performance \>70% * Have documented seropositivity for CMV (either donor or recipient CMV IgG seropositivity) before AHCT. * Eligible for AHCT from an HLA-matched related, matched unrelated, mismatched unrelated or haploidentical donor using either bone marrow or peripheral blood stem cells. * Have undetectable CMV DNA from a plasma sample collected within 5 days prior to enrollment. * Must be within Day-10 thru Day+28 days of planned HSCT at the time of enrollment. * Be able to comply with medical recommendations or follow-up. * Has adequate organ functions determined by 1. Serum creatinine clearance ≥50 ml/min (calculated with Cockroft-Gault formula). 2. Bilirubin ≤1.5 mg/dl except for Gilbert's disease. 3. ALT or AST ≤200 IU/ml for adults. 4. Conjugated (direct) bilirubin \< 2x upper limit of normal. 5. Left ventricular ejection fraction ≥40%. 6. Diffusing capacity for carbon monoxide (DLCO) ≥ 50% predicted corrected for hemoglobin.
Exclusion criteria
* Has a history of CMV end-organ disease or CS-CMVi within 6 months prior to enrollment. * Received within 7 days prior to screening or plans to receive during the study any of the following: 1. Ganciclovir 2. Valganciclovir 3. Foscarnet 4. Acyclovir (\> 3200 mg PO per day or \> 25 mg/kg IV per day) 5. Valacyclovir (\> 3000 mg/day) 6. Famciclovir (\> 1500 mg/day) * Received within 30 days prior to screening or plans to receive during the study any of the following drugs: cidofovir, CMV hyper-immune globulin, any investigational CMV antiviral agent/biologic therapy. * Has suspected or known hypersensitivity to active or inactive ingredients of letermovir formulations. * Has an uncontrolled infection * Requires mechanical ventilation or is hemodynamically unstable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of clinically significant cytomegalovirus infection (CS-CMVi) at 52 weeks after transplant | 1 year after transplant | Number of patients who develop CS-CMVi within 52 weeks after receiving a transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of CMV disease at 52 weeks after transplant | 1 year after transplant | Number of patients who develop CMV disease within 52 weeks after receiving a transplant |
| Cumulative incidence of CMV related death at 52 weeks | 1 year after transplant | Number of patients who die from complications directly attributable to CMV infection within 52 weeks |
| Overall Survival at 1 year after transplant | 1 year after transplant | Number of patients who survive beyond 1 year after transplant |
| Positive predictive value of CMV-TCIP assay after transplant in predicting CS-CMVi protection | 1 year after transplant | Positive predictive value of CMV-TCIP assay at 14 weeks after transplant in predicting CS-CMVi protection through 1 year after transplant in patients who had letermovir discontinuation |
Countries
United States
Contacts
CONTACTChao Family Comprehensive Cancer Center University of California, Irvine
CONTACTUniversity of California Irvine Medical
PRINCIPAL_INVESTIGATORPiyanuch Kongtim, MD,PhD
Chao Family Comprehensive Cancer Center
Outcome results
None listed