Sinusoidal Obstruction Syndrome for Stem Cell Transplant Patients Biomarker Study (SOSBiomarker)

Biomarkers of Endothelial Dysfunction in Pediatric Patients Receiving High Intensity Chemotherapy/Irradiation

The goal of this is to learn more about stem cell transplant and complications that some people have after their transplants, in particular sinusoidal obstruction syndrome (SOS), also called veno-occlusive disease of the liver.

Study Overview

• Status: Completed
• Conditions: Sinusoidal Obstruction Syndrome
• Intervention / Treatment: Other: Serial Blood Draws

Detailed Description

This is a multicenter, prospective, observational trial. We will measure biomarkers and determine thresholds that will predict increased risk for SOS in pediatric patients receiving HCT or high intensity chemotherapy/irradiation with the future goal of a randomized, interventional, open-label, multicenter trial that will test the preemptive use of defibrotide for prevention of SOS in an enriched high-risk population.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Stem Cell Transplant patients

Description

Inclusion Criteria:

Age ≤ 25 years undergoing HCT for any reason who fulfill any ONE (1) of the following criteria:

1. History of hepatic disease as defined by:

   1. Viral hepatitis (i.e., hepatitis C virus [HCV])
   2. Liver tumor before HCT
   3. Hepatic fibrosis or cirrhosis before HCT as proven by liver biopsy
   4. High aspartate aminotransferase (AST) (> 2x ULN) before HCT (pre-transplant evaluation)
   5. High alanine transaminase (ALT) (> 2x ULN) before HCT
   6. High bilirubin (> 1.2x ULN) before HCT

2. HCT high-risk features including:

   a. Conditioning with high-risk modalities including: i. Busulfan (BU)-containing regimen particularly with oral BU + cyclophosphamide ii. TBI-containing regimen, particularly cyclophosphamide + total-body irradiation (TBI) b. ≥ 2 HCT c. Allo-HCT for leukemia > or = second relapse d. Unrelated donor (URD) HCT e. Human leukocyte antigen (HLA) mismatch HCT (less than 10 of 10 for bone marrow/peripheral blood stem cell [BM/PBSC] or anything less than 6 of 6 for UCB) f. Use of sirolimus + tacrolimus prophylaxis for GVHD

3. High-risk disease states including:

   1. Juvenile myelo-monocytic chronic leukemia (JMML)
   2. Primary hemophagocytic lymphohistiocytosis (HLH)
   3. Adrenoleukodystrophy
   4. Osteopetrosis

4. Other high-risk features including:

   1. Prior treatment with gemtuzumab ozogamicin
   2. Use of hepatotoxic drugs 1 month before HCT and during HCT
   3. Iron overload (i.e., thalassemia/sickle cell) with serum ferritin > 1000ng/ml
   4. Deficit of ATIII, T-PA (i.e., < 30% normal values), and resistance to activated protein C if clinical indication (these values do not have to be specifically checked if no clinical history)
   5. Young age < 2 years but more than 1 month

Exclusion Criteria:

Patients who are transplanted but do not fulfill any of the above mentioned criteria.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stem Cell Transplant; Serial Blood Draws	Other: Serial Blood Draws; Day 0 and Day 3 blood draw for SOS biomarkers. If subject develops SOS blood draw prior to dose of Defibrotide, Day 14 after Defibrotide and Day 21 after Defibrotide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SOS proteomic markers	Measure for 3 SOS proteomic markers, L-Ficolin, HA, and ST2, as early predictors of SOS incidence through study completion.	Until the end of the study evaluation, day 180

Collaborators and Investigators

• Sponsor: Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): January 14, 2021
• Study Completion (Actual): January 14, 2021

Study Registration Dates

• First Submitted: April 24, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease; Liver Diseases; Syndrome; Hepatic Veno-Occlusive Disease
• Other Study ID Numbers: 1701020549

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No