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The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation | Clinical Trials | Clareo Health

TERMINATEDPHASE2

The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation

Study to Assess the Safety, Overall Tolerability, and Antiviral Activity of Brincidofovir Versus Standard of Care for Treatment of Adenovirus in High-risk Pediatric Allogeneic Hematopoietic Transplant Recipients

NCT03339401•Jazz Pharmaceuticals

View on ClinicalTrials.gov

Summary

This study was designed to assess the safety, overall tolerability, and antiviral activity of "short course" brincidofovir (BCV) therapy, as compared with current standard of care (SoC), for the treatment of adenovirus (AdV) infections in high-risk (i.e., T cell depleted) pediatric allogeneic hematopoietic cell transplant (HCT) recipients. A virologic response-driven approach to the duration of treatment was to be evaluated, in which subjects randomized to BCV therapy were to be treated until AdV viremia was confirmed as undetectable or until a maximum of 16 weeks of therapy, whichever occurred first. The formulation of BCV used in this study was oral tablet/suspension.

Detailed Description

This was a randomized, open-label, multi-center study of the safety, overall tolerability, and antiviral activity of BCV, as compared with SoC, in pediatric (and young adults in the United States) recipients of high-risk (i.e., T cell-depleted and/or unrelated cord blood graft, or a T cell-replete graft from ahaploidentical donor with post-transplant cyclophosphamide administration) allogeneic HCT. Subjects with AdV detected in plasma after their qualifying transplant could be screened for participation in the study. Subjects who met all applicable entry criteria were randomized in a 2:1 ratio to receive either BCV or SoC (i.e., investigator-assigned therapy). The formulation of BCV used in this study was oral tablet/suspension. Subjects were randomized within 100 days post-transplant; for study purposes, the day of randomization was defined as Day 1. During randomization, subjects were stratified based on the following variables: last AdV viremia (≥10,000 copies/mL versus \<10,000 copies/mL) measurement available from the designated central virology laboratory prior to randomization, time from transplant to randomization (≥28 days versus \<28 days), and T cell-depletion methodology (receipt of alemtuzumab or ex vivo depletion versus receipt of anti-thymocyte globulin \[ATG\] or no T cell depletion).

Eligibility

Age

0 - 25 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Subjects were high-risk allogeneic hematopoietic cell transplant (HCT) recipients aged 2 months to \<18 years (\<26 years in the United States) who met adenovirus (AdV) viremia criteria within 7 days of randomization (Day 1), and all other eligibility criteria. High-risk was defined as having received 1 of the following:
•A T cell-depleted graft:
•* Ex vivo T cell depletion via positive selective (e.g., CD34+ cell) or negative selection (e.g., T cell receptor α/β or CD3+ cell removal by column filtration); or
•* Serotherapy with ATG (cumulative dose of ≥3 mg/kg rabbit-derived ATG or ≥30 mg/kg of equine-derived ATG) administered within 10 days prior to transplant or at any time post-transplant and prior to Day 1; or
•* Serotherapy with alemtuzumab administered within 30 days prior to transplant or at any time post-transplant and prior to Day 1; or
•A cord blood graft from an unrelated donor with or without T cell depletion, or
•A T cell-replete graft from a haploidentical donor with high-dose cyclophosphamide (e.g., cumulative dose of ≥100 mg/kg) administered at any time post-transplant and prior to Day 1.
•Subjects must have had qualifying AdV viremia within 100 days of transplant, which was defined as having either:
•1. Confirmed AdV viremia of ≥1000 copies/mL on 2 consecutive AdV DNA polymerase chain reaction (PCR) test results drawn ≥48 hours apart from the designated central virology laboratory, with the second result being greater than the first; or
•2. A single AdV viremia result of ≥10,000 copies/mL from the designated central virology laboratory Subjects who were previously treated with intravenous (IV) cidofovir (CDV) could have a cumulative exposure to IV CDV of no more than 10 mg/kg within 21 days prior to Day 1.
+1 more criteria

Exclusion Criteria

•1. Any United States National Institutes of Health (NIH)/National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 4 diarrhea (i.e., life-threatening consequences with urgent intervention indicated) within 7 days prior to Day 1.
•2. Any CTCAE Grade 2 or 3 diarrhea (i.e., increase of ≥4 stools/day over baseline \[pre-transplant\] diarrheal output), unless attributed to AdV, within 7 days prior to Day 1.
•3. NIH Stage 4 acute graft versus host disease (GVHD) of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day 1.
•4. NIH Stage ≥2 acute GVHD of the liver (i.e., bilirubin \>3 mg/dL \[SI: \>51 µmol/L\]) within 7 days prior to Day 1.
•5. NIH Stage ≥2 acute GVHD of the gut (i.e., diarrhea \>556 mL/m2/day for pediatric patients \[or \>1000 mL/day for young adults at centers in the United States only\], or severe abdominal pain with or without ileus) within 7 days prior to Day 1.
•6. Poor clinical prognosis (including active malignancy or use of vasopressors other than low dose (e.g., ≤5 µg/kg/min) dopamine for renal perfusion within 7 days prior to Day 1.
•7. Requirement for mechanical ventilation within 7 days prior to Day 1 or requirement for sustained oxygen delivery for \>24 hours within 7 days prior to Day 1.
•8. Concurrent HIV, active hepatitis B virus, or hepatitis C virus infection.
•9. Specified out of range laboratory results (including alanine aminotransferase \>5x the upper limit of normal \[ULN\], aspartate aminotransferase \>5x ULN, total bilirubin \>3 mg/dL \[SI: \>51 µmol/L\], or prothrombin time-international normalized ratio \>2x ULN) within 7 days prior to Day 1.
•10. Estimated creatinine clearance \<30 mL/min or use of renal replacement therapy within 7 days prior to Day 1.
+3 more criteria

Locations (36)

Children's Hospital of Los Angeles

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

University of Chicago

Chicago, Illinois, United States

Joseph M. Sanzari Childrens Hospital-Regional Cancer Care

Hackensack, New Jersey, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

University of Washington-Seattle Childrens Hospital

Seattle, Washington, United States

Key Dates

Start Date

December 22, 2017

Primary Completion Date

May 10, 2019

Completion Date

May 10, 2019

Last Updated

January 25, 2021

Enrollment

ACTUAL participants

Conditions

Adenovirus

Interventions

Standard of Care

OTHER

Brincidofovir

DRUG

Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation

NCT05664126

CytomegalovirusAdenovirus

View study

RECRUITINGPHASE2

Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection

NCT03266627

AdenovirusPrimary Immune Deficiency Disorder

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 25, 2021Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation

Inclusion Criteria

Exclusion Criteria

Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation

Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection

R-MVST Cells for Treatment of Viral Infections in Children and Young Adults

A Study to Assess Safety and Feasibility of Direct Infusions of Donor-derived Virus-specific T-cells in Recipients of Hematopoietic Stem Cell Transplantation With Post-transplant Viral Infections Using the Cytokine Capture System®

Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes (CTL)

Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant