Transplants: Clinical Research Program

Eligibility

• Male or female, Age 1 month – 75 years
• HCT recipients (Auto or Allograft)
• SOS/VOD as defined by Cairo/Cooke Diagnostic criteria (1) (Table 3) with either renal and/or pulmonary dysfunction as defined by Cairo/Cooke Grading criteria (1) (Appendix I)
• Unresponsive to standard defibrotide therapy as defined by at least one of the following:
  • Patients with SOS/VOD failing to obtain a complete response (CR) defined by Grade I or less by Cairo/Cooke Grading criteria (1) (Appendix I). This would therefore include patients with stable disease after at least 14 days of defibrotide or partial response after at least 21 days of defibrotide (25mg/kg/day).
  • Progressive disease defined by progression of at least one grade or more from diagnostic grade as defined by Cairo/Cooke Grading criteria (1) (Appendix I) following at least 7 days of defibrotide (25mg/kg/day).
• Exclusion Criteria
  • Patients who did not receive HCT
  • Concomitant systemic anticoagulation (excluding central venous line management, fibrinolytic instillation for central venous line occlusion, management of intermittent dialysis or ultrafiltration of CVVH)
  • Active bleeding and/or hemorrhage of at least grade 2 and above
  • History of development of Grade III/IV anaphylaxis probably or directly secondary to defibrotide
  • Female patients who are pregnant or breast feeding

Enrollment Status: Actively enrolling

Study Information

ClinicalTrials.gov | NCT05987124

Principal Investigator

Mitchell Cairo, MD

Contact for Study Screening

[email protected]

Inclusion Criteria 

• Male or female, ≥2 years and <18 years at the time of enrollment.
• Weight must be ≥6 kg at the time of enrollment.
• Planned allogeneic HCT (bone marrow, peripheral blood stem cell, or cord blood transplant).
• Patient must be CMV sero-positive (i.e., recipient CMV immunoglobulin G positive).

Note: If a patient has hypogammaglobulinemia but has previously been documented as CMV sero-positive, that is acceptable for study inclusion. For all patients already confirmed to be CMV IgG seropositive, repeat testing is not required within 7 days prior to enrollment (see Section 3.2). However, the laboratory data determining eligibility must be available in the patient’s medical/research record for verification.

• Patient is eligible for entry only if it is feasible for plasma CMV PCR testing to be sent and resulted within the protocol mandated time period.

Reminder: To limit the likelihood of positive plasma CMV PCR post-enrollment and prior to start of study treatment period, it is recommended that patient enrollment proceed after patients start their transplant preparative regimen.

• Patient must have a performance status corresponding to Lansky/Karnofsky scores > 50.

Note: Use Lansky for patients ≤ 16 years of age and Karnofsky for patients > 16 years of age. For further reference, see Performance Status Scales Scoring under the Standard Sections for Protocols among Protocol Reference Materials provided on the COG Member Website: https://members.childrensoncologygroup.org/prot/reference_materials.asp

• Adequate renal function defined as an estimated glomerular filtration rate > 10 mL/min/1.73 m2 and not receiving dialysis.
• Adequate liver function defined as:
• Direct bilirubin ≤ 2 mg/dL and SPGT (ALT) ≤ 10 x upper limit of normal (ULN) for age.

Exclusion Criteria 

• Expected inability to tolerate oral formulations of Letermovir.
• Hypersensitivity to letermovir or any component of the formulation.
• History of CMV end organ disease within 6 months (180 days) prior to enrollment.
• Receipt of prior allogeneic HCT within one year of study enrollment.
• Planned prophylactic administration of other anti-CMV medications or cellular products during the study, including:

• High dose acyclovir (defined as doses >= 1500 mg/m^2 IV or >= 3200 mg oral (patients >= 40 kg) or >= 2400 mg/m^2 (patients < 40 kg) per day)
• High dose valacyclovir (defined as doses >= 3000 mg/day in patients > 20 kg)
• Foscarnet
• Ganciclovir
• Valganciclovir
• CMV-directed cytotoxic T lymphocytes

• Planned receipt of the following contraindicated medications during the study treatment period; contraindicated medications must be discontinued at least 14 days prior to Day +1.
• Contraindicated medications for all patients:
• Pimozide
• Ergot alkaloids
• Contraindicated medications for patients planned to receive cyclosporine:
• Bosentan
• Pitavastatin
• Simvastatin
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted in certain animal reproduction studies with letermovir. A pregnancy test is required for female patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active female patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their letermovir treatment and through at least 4 weeks after the last dose of letermovir.
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Enrollment Status: Open to Enrollment

Study Information: NCT05711667

Principal Investigator: Andrew Bellantoni, MD

Contact for Study Screening: [email protected]