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A Study of the Drug Letermovir (LTV) as Prevention for Recurrent of Cytomegalovirus (CMV) Infection

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ClinicalTrials.gov Identifier: NCT04017962
Recruitment Status : Recruiting
First Posted : July 12, 2019
Last Update Posted : October 10, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to determine of letermovir (LTC) is effective at preventing Cytomegalovirus (CMV) infection from returning in people who have already had CMV infection after a bone marrow transplant.

Condition or disease Intervention/treatment Phase
CMV CMV Infection Hematopoietic Cell Transplant Drug: Letermovir Pill Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Single-arm Study of Letermovir (LTV) for Prevention of Recurrent CMV Infection in High-risk Hematopoietic Cell Transplant (HCT) Recipients
Actual Study Start Date : July 19, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Letermovir

Arm Intervention/treatment
Experimental: Hematopoietic cell transplantation/HCT
Participants will be hematopoietic cell transplantation (HCT) recipients with a history of CMV infection.
Drug: Letermovir Pill
Patients enrolled on the study will receive oral LTV 480 mg daily (240 mg daily for patients receiving cyclosporine A). The maximum duration of LTV administration will be 14 weeks.
Other Name: LTV




Primary Outcome Measures :
  1. The rate of breakthrough clinically significant Cytomegalovirus (CMV) infection by week 14 [ Time Frame: up to 24 weeks from time of study treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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. Clinically significant CMV infection is defined as CMV viremia requiring preemptive therapy or CMV EOD. Patients who received LTV prophylaxis prior to onset of clinically significant CMV infection prior to enrollment.
  • Undetectable or low CMV viral load at the time of enrollment, defined as at least two consecutive measurements </=300 IU/mL or at least one undetectable measurement, providing the prior measurements showed a consistent decline in viral load with the last specimen </= 7 days prior to Day 1.
  • Have one or more risk factors for recurrent CMV infection:

    1. 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
    2. 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
    3. T-cell-depleted allograft
  • 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
  • T-cell count >/=100 at day +100

Exclusion Criteria:

  • Clinically significant CMV infection present at enrollment
  • Breakthrough CMV infection while on primary LTV prophylaxis (unless patient non-adherent to prophylaxis) or presence of documented resistance to LTV.
  • Glomerular filtration rate (GFR) </= mL/min/1.73m^2(equivalent to creatinine clearance </=10 mL/min)
  • Severe hepatic impairment (Child Pugh C)
  • 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.

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) prior to enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04017962


Contacts
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Contact: Genovefa Papanicolaou, MD 347-501-0044 papanicg@mskcc.org
Contact: Yeon Joo Lee, MD 212-639-8180 leey3@mskcc.org

Locations
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United States, New York
Memorial Sloan - Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Genovefa Papanicolaou, MD    347-501-0044      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Genovefa Papanicolaou Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04017962     History of Changes
Other Study ID Numbers: 19-174
First Posted: July 12, 2019    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: • Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
HCT
CMV infection
Letermovir
LTV
Memorial Sloan Kettering Cancer Center
19-174
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases