Prospect Eval of Efficacy of CMV-TCIP Direct Letermovir Prophylax After Allogen Hemato Cell Transpla

Allogeneic Stem Cell Transplantation Clinical Trial

Official title:

Prospective Evaluation of Efficacy of CMV-specific T Cell Immunity (CMV-TCIP) Directed Letermovir Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06453460
• Other study ID #: 4005
• Secondary ID: UCI 22-188
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: June 2029

Study information

• Verified date: June 2024
• Source: University of California, Irvine
• Contact: Chao Family Comprehensive Cancer Center University of California
• Phone: 1-877-827-8839
• Email: ucstudy[@]uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: June 2029
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.
• Be within 28 days post-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 on the day of randomization.
• Requires mechanical ventilation or is hemodynamically unstable at the time of randomization.

Related Conditions & MeSH terms

• Allogeneic Stem Cell Transplantation
• CMV

Intervention

Drug:
• Letermovir
Subjects will receive 14 weeks of letermovir prophylaxis at standard recommended dose follow by CMV-TCIP-directed extended prophylaxis.

Device:
• CMV 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 Test:
• CMV 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.

Locations

Country	Name	City	State
United States	Chao Family Comprehensive Cancer Center, University of California Irvine	Orange	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Irvine	Eurofins Viracor

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative incidence of clinically significant cytomegalovirus infection (CS-CMVi) at 52 weeks after transplant	Number of patients who develop CS-CMVi within 52 weeks after receiving a transplant	1 year after transplant
Secondary	Cumulative incidence of CMV disease at 52 weeks after transplant	Number of patients who develop CMV disease within 52 weeks after receiving a transplant	1 year after transplant
Secondary	Cumulative incidence of CMV related death at 52 weeks	Number of patients who die from complications directly attributable to CMV infection within 52 weeks	1 year after transplant
Secondary	Overall Survival at 1 year after transplant	Number of patients who survive beyond 1 year after transplant	1 year after transplant
Secondary	Positive predictive value of CMV-TCIP assay after transplant in predicting CS-CMVi protection	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	1 year after transplant