Clinical trial NCT02204904: Observational Study to Evaluate Allogeneic HSCT Outcomes for Cerebral Adrenoleukodystrophy (CALD)
Official title: A Prospective and Retrospective Data Collection Study to Evaluate Outcomes in Males ≤17 Years of Age Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Cerebral Adrenoleukodystrophy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: X-Linked Adrenoleukodystrophy (X-ALD)
Cerebral Adrenoleukodystrophy (CALD)
Adrenoleukodystrophy (ALD)
Keywords: X-linked Adrenoleukodystrophy
Hematopoietic Stem Cells
Lead sponsor: bluebird bio
Sponsor class: INDUSTRY
First posted: 2014-07-31
Enrollment: 59
Sex: MALE
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Boys aged 17 or younger receiving allogeneic hematopoietic stem cell transplantation for the treatment of cerebral adrenoleukodystrophy prospectively or partially prospective/retrospective

Brief summary: Study ALD-103 will be a multi-site, global, prospective and retrospective data collection study that is designed to evaluate outcomes of allo-HSCT in male subjects with CALD ≤17 years of age.


Eligibility criteria: Inclusion Criteria:

1. Provide informed consent from a competent custodial parent or guardian with legal capacity to execute a local Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved consent. In addition, informed assent will be sought from capable subjects, in accordance with the directive of the institution's IRB/IEC and all other local requirements.
2. Be male and ≤17 years of age at the time of treatment, for retrospective and partial prospective/retrospective subjects, or at the time of parental/guardian consent and, where appropriate, subject assent, for prospective subjects.
3. Have a confirmed diagnosis of CALD as defined by abnormal VLCFA profile and cerebral lesion on brain MRI.
4. Depending on the cohort, the subject must:

   * Be scheduled for allo-HSCT evaluation at a study site (prospective cohort only),
   * Have received an allo-HSC infusion and be consented in time to complete the Month 24 Visit on study (partial prospective/retrospective cohort only), or
   * Have received their most recent allo-HSC infusion on or after January 1, 2013 (retrospective cohort only).

Exclusion Criteria:

1. Previous treatment with a gene therapy product.
2. Receipt of an experimental transplantation procedure.

Primary outcomes:
measure: Incidence of transplant-related mortality (TRM).
timeFrame: Through 100 and 365 days post allo-HSC infusion
measure: Incidence and timing of neutrophil engraftment.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence and timing of platelet engraftment
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of engraftment failure or allograft rejection.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of primary donor-derived chimerism of ≥50%.
timeFrame: by 100 days post allo-HSC infusion
measure: Frequency and severity of Criteria for Adverse Events (CTCAE) ≥Grade 3 AEs, CTCAE ≥Grade 3 infections, and all SAEs.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Proportion of subjects who experience either ≥Grade II acute (Graft versus Host Disease) GVHD or chronic GVHD.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of ≥Grade II acute GVHD.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Incidence of chronic GVHD.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Number of emergency room visits.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Number and duration of intensive care unit stay.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
measure: Number and duration of in-patient hospitalization.
timeFrame: 1-48 (± 1) months post allo-HSC infusion
Secondary outcomes:
measure: Incidence of Major Functional Disabilities (MFDs).
timeFrame: 1-48 (± 2) months post allo-HSC infusion
measure: Change from Baseline in Loes score
timeFrame: 1-48 (± 2) months post allo-HSC infusion
measure: Change from Baseline in Neurological Function Score (NFS)
timeFrame: 1-48 (± 2) months post allo-HSC infusion
measure: Frequency and timing of resolution of gadolinium enhancement on MRI, if applicable
timeFrame: 1-48 (± 2) months post allo-HSC infusion
measure: MFD-free survival
timeFrame: 48 (± 2) months post allo-HSC infusion
measure: Overall survival
timeFrame: 48 (± 2) months post allo-HSC infusion
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Boston
country: United States
facility: Boston Children's Hospital/Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Buenos Aires
country: Argentina
facility: Hospital Austral
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambine Gesú
city: Utrecht
country: Netherlands
facility: Princess Maxima Center for Pediatric Oncology (PMC)
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust
Study officials:
affiliation: bluebird bio, Inc.
name: Elizabeth McNeil, MD MSc
role: STUDY_DIRECTOR
References:
citation: Chiesa R, Boelens JJ, Duncan CN, Kuhl JS, Sevin C, Kapoor N, Prasad VK, Lindemans CA, Jones SA, Amartino HM, Algeri M, Bunin N, Diaz-de-Heredia C, Loes DJ, Shamir E, Timm A, McNeil E, Dietz AC, Orchard PJ. Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy. Blood Adv. 2022 Mar 8;6(5):1512-1524. doi: 10.1182/bloodadvances.2021005294.