CMV-TCIP Directed Letermovir Prophylaxis After Allo-SCT

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

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.

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