Cord Blood Infusion for Children With Autism Spectrum Disorder
Condition: Autism Spectrum Disorder; ASD; Autism; PDD
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Intervention: Cord Blood Infusion; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 180.0
Sex: All
Minimum age: 2 Years
Maximum age: 7 Years
Healthy volunteers: No

Summary:

      This is a single site, prospective, randomized, double-blind study of a single intravenous
      autologous or allogeneic, unrelated cord blood (CB) infusion in children ages 2-7 years with
      Autism Spectrum Disorder (ASD). Participants will be randomly assigned to Sequence A,
      consisting of a single infusion of CB cells at baseline followed 6 months later by a single
      infusion of placebo, or Sequence B, consisting of an infusion of placebo at baseline followed
      6 months later by an infusion of CB cells. All participants will ultimately be treated with
      CB cells at some point during the study. Participants with an available qualified autologous
      CB unit will receive autologous cells, and those without a suitable autologous CB unit
      available will receive cells from a ≥4/6 HLA-matched, ABO-matched allogeneic, unrelated donor
      CB unit from the Carolinas Cord Blood Bank. All infusions will be double-blinded. The primary
      outcomes will be assessed 6 months after the initial infusion in the sequence. Additional
      testing for secondary exploratory analyses will be performed at 12 months. Duration of study
      participation will be 12 months from the time of baseline infusion.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 2 years to ≤ 7 years (7 years, 364 days) at the time of visit 1

          2. Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using the DSM-5
             Checklist

          3. Fragile X testing performed and negative

          4. Available and qualified umbilical cord blood unit with a minimum banked total
             nucleated cell dose of ≥ 2.5 x 107 cells/kg that meets criteria outlined in Section
             6.0, either:

               -  Autologous umbilical cord blood unit OR

               -  ≥4/6 HLA-matched and ABO/Rh-matched allogeneic unrelated umbilical cord blood
                  unit from the Carolinas Cord Blood Bank

          5. Stable on current psychiatric medication regimen (dose and dosing schedule) for at
             least 2 months prior to infusion of study product

          6. Normal absolute lymphocyte count (≥1500/uL)

          7. Participant and parent/guardian are English speaking

          8. Able to travel to Duke University two times (baseline and 6 months post-baseline), and
             parent/guardian is able to participate in interim surveys and interviews

          9. Parental consent

        Exclusion Criteria:

          1. General:

               -  Review of medical records indicates ASD diagnosis not likely

               -  Known diagnosis of any of the following coexisting psychiatric conditions:
                  depression, bipolar disorder, schizophrenia, obsessive compulsive disorder,
                  Tourette syndrome

               -  Screening data suggests that participant would not be able to comply with the
                  requirements of the study procedures, including study outcome measures, as
                  assessed by the study team

               -  Family is unwilling or unable to commit to participation in all study-related
                  assessments, including follow up for approximately 12 months

               -  Sibling is enrolled in this (DukeACT) study

          2. Genetic:

               -  Records indicate that child has a known genetic syndrome such as (but not limited
                  to) Fragile X syndrome, neurofibromatosis, Rett syndrome, tuberous sclerosis,
                  PTEN mutation, cystic fibrosis, muscular dystrophy b. Known pathogenic copy
                  number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)

          3. Infectious:

               -  Known active central nervous system infection

               -  Evidence of uncontrolled infection based on records or clinical assessment

               -  HIV positivity

          4. Medical:

               -  Known metabolic disorder

               -  Known mitochondrial dysfunction

               -  History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms,
                  Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure
                  disorder

               -  Active malignancy or prior malignancy that was treated with chemotherapy

               -  History of a primary immunodeficiency disorder

               -  History of autoimmune cytopenias (i.e., ITP, AIHA)

               -  Coexisting medical condition that would place the child at increased risk for
                  complications of sedation or other study procedures

               -  Concurrent genetic or acquired disease or comorbidity(ies) that could require a
                  future stem cell transplant

               -  Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment)
                  or motor (e.g., cerebral palsy) impairment

               -  Impaired renal or liver function as determined by serum creatinine >1.5mg/dL or
                  total bilirubin >1.3mg/dL, except in patients with known Gilbert's disease

               -  Significant hematologic abnormalities defined as: Hemoglobin <10.0 g/dL, White
                  blood count < 3,000 cells/mL, absolute lymphocyte count <1000/uL, Platelets <150
                  x 10e9/uL

               -  Evidence of clinically relevant physical dysmorphology indicative of a genetic
                  syndrome as assessed by the PIs or other investigators, including a medical
                  geneticist or psychiatrists trained in identifying dysmorphic features associated
                  with neurodevelopmental conditions

          5. Current/Prior Therapy:

               -  History of prior cell therapy

               -  Current or prior use of immune globulins or other anti-inflammatory medications
                  with the exception of non steroidal anti-inflammatory medications

               -  Current or prior immunosuppressive therapy

               -  No systemic steroid therapy that has lasted >2 weeks, and no systemic steroids
                  within 3 months prior to enrollment. Topical and inhaled steroids are permitted.