An Open-label, Single-arm Study of Letermovir (LTV) for Prevention of Recurrent CMV Infection in High-risk Hematopoietic Cell Transplant (HCT) Recipients
Recruiting
This is an open-label single arm trial of letermovir (LTV, Prevymis) for prevention of recurrent CMV infection in allogeneic hematopoietic cell transplantation (HCT) recipients with history of
CMV infection. The study is being conducted at MSKCC and at the University of Minnesota.
Thirty-six HCT recipients who are ≥12 years of age, had clinically significant CMV infection
treated with CMV antivirals and are at high risk for recurrent CMV infection, defined as
receiving a transplant from an HLA mismatched donor (including cord blood), acute or chronic graft versus host disease (GVHD) requiring either topical and/or systemic steroid treatment within 14 days prior to enrollment, or T cell-depleted (CD34+-selected) allograft, will be eligible to participate in the study.
Age >/= 12 years (any weight)
Have received allogenic HCT
Have received preemptive therapy for clinically significant CMV infection post-HCT and have completed preemptive therapy no longer than 7 days prior to enrollment. Preemptive treatment includes ganciclovir, valganciclovir, foscarnet or cidofovir. Clinically significant CMV infection is defined as CMV viremia requiring preemptive therapy or CMV EOD. Patients who have received LTV prophylaxis prior to onset of clinically significant CMV infection prior to enrollment (see also exclusion criteria below).
Have one or more risk factors for recurrent CMV infection:
Human leukocyte antigen (HLA) mismatch
HLA-related (sibling) donor with at least one mismatch at the HLA-A, -B or -DR gene loci
Haploidentical donor
Unrelated donor with at least one mismatch at the HLA-A, -B, -C or -DRC1gene loci, or
Cord blood as stem cell source
Acute or chronic GVHD requiring either topical steroids for gastrointestinal GVHD and/or systemic steroid treatment (>/= 1mg/kg/day of prednisone or equivalent dose of another corticosteroid) within 14 days prior to enrollment
T-cell-depleted allograft ex-vivo or in-vivo T-cell depleting agents including but not limited to ATG, alemtuzimab and post HCT cyclophosphamide.
For adult patients, able to provide written consent and complete the informed consent. For patients under 18 years, the patient's parent(s) or legal guardian(s) must provide informed consent and the patient must provide written assent to participation in the study.
Willing and able to comply with trial instructions and requirements
Male and female patients of childbearing potential must be willing to use a highly effective method of contraception for the course of the study. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
Subject eligibility criteria for the observational cohort:
Age 18 years or older
First allogenic peripheral blood or marrow HCT
LTV prophylaxis starting <30 days post HCT and given for at least 6 weeks
Exclusion Criteria:
Clinically significant CMV infection present at enrollment
Breakthrough CMV infection while on primary LTV prophylaxis (unless patient non-adherent or unable to adequately absorb letermovir or documented resistance to LTV.
Glomerular filtration rate (GFR) = mL/min/1.73m^2(equivalent to creatinine clearance =10 mL/min)
Severe hepatic impairment
Routine use of high-dose acyclovir (doses of > 800 mg twice daily), valacyclovir (doses of > 500mg twice daily), or famciclovir (doses > 500mg/day) for varicella zoster virus (VZV)/herpes simplex virus prophylaxis; limited treatment courses at higher doses for VZV infections are permissible if treatment duration dose not exceed 14 days total. Short courses of IV cidofovir for adeno virus (ADV) are permissible
Suspected or known hypersensitivity to active or inactive ingredients of LTV formulations
Patients treated with a medication whose administration with LTV is ontraindicated and whose discontinuation is not possible. Contraindicated medications include pimozide, ergot alkaloids and pitavastatin or simvastatin when co-administered with cyclosporine.
Imminent demise (expected survival <6 weeks)
Documented positive result for human immunodeficiency virus antibody (HIV-Ab) or for hepatitis C virus antibody (HCV-Ab) with detectable HCV RNA, or hepatitis B surface antigen (HBsAg) at any time prior to HCT
Need for mechanical ventilation and/or vasopressor support at the time of enrollment
Pregnancy or breastfeeding
Plans to conceive or father children within the projected duration of the trial
History of current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or would place the subject at undue risk as judged by the investigator, such that it is not in the best interest of the subject to participate in this study.
The following antivirals are allowed up to the listed dose limits:
Acyclovir up to 800 mg twice daily
Valacyclovir up to 500 mg twice daily
Famciclovir up to 500 mg/day for VZV/HSV prophylaxis; limited treatment courses at higher doses for VZV infections are permissible if treatment duration does not exceed 14 days total.
Short courses of IV cidofovir for ADV (up to two doses)
Exclusion criteria for observational cohort:
Clinically significant CMV infection during the 100 days following HCT. Clinically significant CMV infection defined as either CMV viremia requiring preemptive therapy with CMV antivirals or CMV end organ disease (EOD)
Grade 3-4 GVHD
Cord blood as cell source for HCT
Treatment with systemic steroids (>0.5mg/kg for 2 weeks or longer) within 3 weeks prior to enrollment
Thank you for choosing StudyFinder. Please visit http://studyfinder.umn.edu to find a Study which is right for you and contact sfinder@umn.edu if you have questions or need assistance.