Trial Title:
A Study of the Drug Letermovir as Prevention of Cytomegalovirus Infection After Stem Cell Transplant in Pediatric Patients
NCT ID:
NCT05711667
Condition:
Hematopoietic and Lymphoid Cell Neoplasm
Malignant Solid Neoplasm
Conditions: Official terms:
Neoplasms
Acetic Acid
Letermovir
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Prevention
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
ARM I (Letermovir prophylaxis)
Arm group label:
ARM II (No prophylaxis)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Letermovir
Description:
Given PO or IV
Arm group label:
ARM I (Letermovir prophylaxis)
Other name:
2-((4S)-8-Fluoro-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)-4H-quinazolin-4-yl)acetic Acid
Other name:
AIC246
Other name:
MK-8228
Other name:
Prevymis
Summary:
This phase III trial determines whether taking prophylactic letermovir will reduce the
likelihood of infection with cytomegalovirus (CMV) in children and adolescents after stem
cell transplant. The treatments used to prepare for HCT reduce the body's natural
infection-fighting ability and increase the likelihood of an infection with a virus
called cytomegalovirus. "Prophylaxis" means to take a drug to prevent a disease or side
effect. Letermovir is an antiviral drug that stops cytomegalovirus from multiplying and
may prevent cytomegalovirus infection and make the disease less severe.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the efficacy of letermovir compared to no prophylaxis in the prevention of
clinically significant cytomegalovirus (CMV) infection through Week 14 (~100 days)
post-transplant in children and adolescents receiving allogeneic hematopoietic cell
transplant (allo-HCT).
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of letermovir compared to no prophylaxis as assessed by time
to onset of any CMV DNAemia through week 14 (~100 days) post transplant.
II. To evaluate CMV-free survival through 24 weeks post transplant in pediatric patients
who receive letermovir compared to those who do not.
EXPLORATORY OBJECTIVES:
I. To evaluate the efficacy of letermovir as assessed by time to onset of clinically
significant CMV infection through weeks 24 (~6 months) and 48 (~1 year) post-transplant.
II. To evaluate overall survival through weeks 24 and 48 post-transplant in patients who
receive letermovir versus those who do not.
III. To compare time to engraftment and describe the cumulative incidence of
non-engraftment among patients who receive letermovir and those who do not.
IV. To examine the rates of several clinically significant adverse events among patients
exposed to letermovir versus those who are not including: the total duration of
neutropenia through week 14 (~100 days) post-transplant, the cumulative incidence of
acute kidney injury and chronic kidney disease by 52 weeks post-transplant, and total
inpatient hospital days by 14 weeks (~100 days) and 52 weeks post-transplant.
V. Describe patterns of anti-viral resistance at the onset of CMV DNAemia after allo-HCT.
VI. To compare immune reconstitution and CMV-specific immunity in pediatric patients
treated with letermovir prophylaxis versus no prophylaxis.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive letermovir orally (PO) or intravenously (IV) over 60 minutes once
daily (QD) starting on day +1 post-transplant for 14 weeks. Patients undergo collection
of blood samples for CMV polymerase chain reaction (PCR) analysis weekly for 14 weeks,
every 2 weeks until week 24, week 32, week 40 and week 52.
ARM B: Patients undergo collection of blood samples for CMV PCR analysis weekly for 14
weeks, every 2 weeks until week 24, week 32, week 40 and week 52.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- >= 2 years and < 18 years at the time of enrollment
- Weight must be >= 18 kg. For patients < 12 years of age and expected to receive
cyclosporine, weight must be >= 30kg
- 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)
- 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 Children's Oncology Group (COG) member website:
https://members.childrensoncologygroup.org/prot/reference_materials.asp
- Estimated glomerular filtration rate > 15 mL/min/1.73 m^2 and not receiving dialysis
- Total bilirubin =< 2.5 mg/dL and serum glutamate-pyruvate transaminase (SPGT)
(alanine transaminase [ALT]) =<10 x upper limit of normal (ULN) for age
- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
Exclusion Criteria:
- Expected inability to tolerate oral formulation (e.g., unable swallow whole tablets)
of letermovir
- Note: Determination of ability to tolerate the oral formulation will be based
on a self-assessment or caregiver assessment; eligible subjects and their
caregiver will be shown a life size picture of a tablet (or actual tablet) and
confirm ability to swallow whole tablet in order to meet study eligibility
- Hypersensitivity to letermovir or any component of the formulation
- History of CMV end organ disease within 6 months (180 days) prior to enrollment
- Note: CMV end organ disease based on proposed definitions by Ljungman et al.
and inclusive of proven, probable or possible disease
- 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
- Lovastatin
- Pitavastatin
- Rosuvastatin
- 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.
- Note: No contraception measures are needed specifically during letermovir
treatment for male trial participants who have pregnant or non-pregnant female
partner(s) of reproductive potential. Contraception measures may be required
for other aspects of the HCT procedure.
- 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
Gender:
All
Minimum age:
2 Years
Maximum age:
18 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Children's Hospital of Alabama
Address:
City:
Birmingham
Zip:
35233
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
205-638-9285
Email:
oncologyresearch@peds.uab.edu
Investigator:
Last name:
Joseph H. Chewning
Email:
Principal Investigator
Facility:
Name:
UCSF Benioff Children's Hospital Oakland
Address:
City:
Oakland
Zip:
94609
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
510-428-3264
Email:
cogbchoak@ucsf.edu
Investigator:
Last name:
Nahal R. Lalefar
Email:
Principal Investigator
Facility:
Name:
Alfred I duPont Hospital for Children
Address:
City:
Wilmington
Zip:
19803
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
302-651-5572
Email:
Allison.bruce@nemours.org
Investigator:
Last name:
Scott M. Bradfield
Email:
Principal Investigator
Facility:
Name:
Nemours Children's Clinic-Jacksonville
Address:
City:
Jacksonville
Zip:
32207
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
302-651-5572
Email:
Allison.bruce@nemours.org
Investigator:
Last name:
Scott M. Bradfield
Email:
Principal Investigator
Facility:
Name:
University of Iowa/Holden Comprehensive Cancer Center
Address:
City:
Iowa City
Zip:
52242
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-237-1225
Investigator:
Last name:
Rajat Sharma
Email:
Principal Investigator
Facility:
Name:
Children's Hospital New Orleans
Address:
City:
New Orleans
Zip:
70118
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Email:
CHResearch@lcmchealth.org
Investigator:
Last name:
Lolie C. Yu
Email:
Principal Investigator
Facility:
Name:
Johns Hopkins University/Sidney Kimmel Cancer Center
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
410-955-8804
Email:
jhcccro@jhmi.edu
Investigator:
Last name:
Heather J. Symons
Email:
Principal Investigator
Facility:
Name:
Children's Hospital of Michigan
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Email:
helpdesk@childrensoncologygroup.org
Investigator:
Last name:
Erin Goode
Email:
Principal Investigator
Facility:
Name:
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Address:
City:
Grand Rapids
Zip:
49503
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
616-267-1925
Email:
crcwm-regulatory@crcwm.org
Investigator:
Last name:
Kathleen J. Yost
Email:
Principal Investigator
Facility:
Name:
Children's Hospital of Philadelphia
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
267-425-5544
Email:
CancerTrials@email.chop.edu
Investigator:
Last name:
Caitlin W. Elgarten
Email:
Principal Investigator
Facility:
Name:
Saint Jude Children's Research Hospital
Address:
City:
Memphis
Zip:
38105
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-226-4343
Email:
referralinfo@stjude.org
Investigator:
Last name:
Diego R. Hijano
Email:
Principal Investigator
Facility:
Name:
The Children's Hospital at TriStar Centennial
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
615-342-1919
Investigator:
Last name:
Jennifer A. Domm
Email:
Principal Investigator
Facility:
Name:
Medical City Dallas Hospital
Address:
City:
Dallas
Zip:
75230
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
972-566-5588
Investigator:
Last name:
Stanton C. Goldman
Email:
Principal Investigator
Facility:
Name:
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
713-798-1354
Email:
burton@bcm.edu
Investigator:
Last name:
Anil George
Email:
Principal Investigator
Facility:
Name:
Methodist Children's Hospital of South Texas
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
210-575-6240
Email:
Vinod.GidvaniDiaz@hcahealthcare.com
Investigator:
Last name:
Jose M. Esquilin
Email:
Principal Investigator
Facility:
Name:
Virginia Commonwealth University/Massey Cancer Center
Address:
City:
Richmond
Zip:
23298
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Email:
CTOclinops@vcu.edu
Investigator:
Last name:
Elizabeth Krieger
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center - University Hospital
Address:
City:
Madison
Zip:
53792
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-622-8922
Email:
clinicaltrials@cancer.wisc.edu
Investigator:
Last name:
Christian M. Capitini
Email:
Principal Investigator
Start date:
May 20, 2024
Completion date:
June 1, 2028
Lead sponsor:
Agency:
Children's Oncology Group
Agency class:
Other
Source:
Children's Oncology Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05711667
