Clinical trial NCT03132337: Sinusoidal Obstruction Syndrome for Stem Cell Transplant Patients Biomarker Study
Official title: Biomarkers of Endothelial Dysfunction in Pediatric Patients Receiving High Intensity Chemotherapy/Irradiation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sinusoidal Obstruction Syndrome
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2017-04-27
Enrollment: 80
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Stem Cell Transplant patients

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: SOS proteomic markers
timeFrame: Until the end of the study evaluation, day 180
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References: