None listed
Conditions
Brief summary
This trial aims to assess the safety and feasibility of using allogeneic UCBCs in preterm infants with severe brain injury. The primary objectives include evaluating the availability of at least 4/6 HLA-matched allogeneic UCBCs for more than 60% of eligible infants and assessing the safety of UCBCs administration by monitoring adverse events and the absence of graft versus host disease (GVHD). Secondary objectives involve evaluating the impact of UCBC administration on short and long-term clinical outcomes, such as death, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, sepsis, developmental delay, cerebral palsy, blindness, and deafness. Additionally, the trial aims to assess the effect of UCBCs on immune responses by measuring cytokine levels. The study will enroll 20 preterm infants with severe brain injury, divided into two strata based on gestational age. The infants will receive one intravenous infusion of 4/6 or higher HLA-matched allogeneic UCBCs obtained from the BMDI Cord Blood Bank at a dose of 50 million cells per kg. The trial will span 3-5 years, including a 24-month post-intervention follow-up period. The recruitment will be limited to Monash Children's Hospital.
Interventions
Summary of intervention: One intravenous infusion of 4/6 or higher Human leucocyte antigen (HLA)-matched allogeneic Umbilical Cord Blood Cells (UCBCs) obtained from Bone Marrow Donor Institute (BMDI) Cord Blood Bank at an approximate dose of 50 million cells per kilogram (as available).
20 preterm infants, with 10 each in each stratum (<28 weeks, ALLO-1 trial and 28 to 36+6 weeks, ALLO-2 trial), will be enrolled.
1. HLA matching: Allogeneic UCBCs will be obtained from BMDI Cord Blood Bank w
Summary of intervention: One intravenous infusion of 4/6 or higher Human leucocyte antigen (HLA)-matched allogeneic Umbilical Cord Blood Cells (UCBCs) obtained from Bone Marrow Donor Institute (BMDI) Cord Blood Bank at an approximate dose of 50 million cells per kilogram (as available). 20 preterm infants, with 10 each in each stratum (<28 weeks, ALLO-1 trial and 28 to 36+6 weeks, ALLO-2 trial), will be enrolled. 1. HLA matching: Allogeneic UCBCs will be obtained from BMDI Cord Blood Bank with an HLA matching of at least 4/6 HLA. The donor UCBCs must match a minimum of 4 out of 6 HLA markers in the recipient. As HLA matching and processing UCBCs may be time-consuming, the eligibility (cranial ultrasound) will be reconfirmed before administering the allogeneic UCBCs after successful HLA matching. 2. Age of administration: Allogeneic UCBCs will be administered via IV infusion anytime from birth until three months of life, generally within 2-3 weeks of diagnosis of severe preterm brain injury. 3. Cell infusion: Only one allogeneic UCBC infusion will be administered intravenously by the nurse in the neonatal intensive care unit under the supervision of the doctor. The doctor will monitor the baby for any adverse events during the infusion and ensure the infusion is provided and completed as per the protocol and standard operating procedures. 4. UCBC dose: At least 50 million total nucleated cells (TNCs) per kilogram of body weight will be administered. This therapeutic dose is based on preclinical and clinical studies of UCBCs for different types of perinatal brain injury. 5. Route: The UCBCs will be administered intravenously via a peripheral intravenous cannula over 1-hour duration.
Sponsors
Monash Children's Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
22 Weeks to 36 Weeks
Healthy volunteers
No
Inclusion criteria
1. Preterm infants born before 28 completed weeks of gestation (up to 27+6 weeks, ALLO-1 trial) OR born between 28 and 36+6 weeks of gestation (ALLO-2 trial) AND 2. Severe brain injury detected on neonatal neuroimaging any time after birth. A severe brain injury will be considered as grade 3 (intraventricular haemorrhage with ventricular distension) or 4 (parenchymal haemorrhagic infarct) IVH and diffuse cystic (grade 3) periventricular leucomalacia.
Exclusion criteria
1. Infants with known major congenital anomalies 2. Infants whose care is being redirected to comfort care. Cell therapy will only be administered when preterm infants are clinically stable, which is deemed by the treating physician. Also, infants should not be receiving antimicrobial therapy for confirmed or presumed late-onset neonatal sepsis at the time of cell infusion as their course may be unpredictable and may confound adverse events falsely attributing to the cell therapy.
Outcome results
None listed