Observational Study to Evaluate Allogeneic HSCT Outcomes for Cerebral Adrenoleukodystrophy (CALD)

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 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.

Study Overview

• Status: Terminated
• Conditions: Cerebral Adrenoleukodystrophy (CALD); Adrenoleukodystrophy (ALD); X-Linked Adrenoleukodystrophy (X-ALD)
• Intervention / Treatment: Genetic: Allo-HSCT

• Study Type: Observational
• Enrollment (Actual): 59

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Austral
• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3H 2R9
      • McGill University Health Centre
• Germany
  • Leipzig, Germany
    • University Hospital Leipzig
• Italy
  • Roma, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambine Gesú
• Netherlands
  • Utrecht, Netherlands
    • Princess Maxima Center for Pediatric Oncology (PMC)
• United Kingdom
  • London, United Kingdom
    • Great Ormond Street Hospital
  • Manchester, United Kingdom, M13 9WL
    • Central Manchester University Hospitals NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Massachusetts
    • Boston, Massachusetts, United States, 02141
      • Boston Children's Hospital/Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• 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

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Allo-HSCT prospective; Subjects who will be consented before they received an allo-HSC infusion. They will be consented and enrolled on the study during the Screening Period.	Genetic: Allo-HSCT; Allogeneic Hematopoietic Stem Cell Transplantation
Allo-HSCT partial prospective/retrospective; Subjects who will be consented after they received an allo-HSC infusion but before they reach 24 months post-infusion on study. Subjects in this cohort will participate prospectively in at least the Month 24 Visit in order to obtain prospective on-study data for this and all visits after Month 24	Genetic: Allo-HSCT; Allogeneic Hematopoietic Stem Cell Transplantation
Allo-HSCT retrospective; Subjects who received an allo-HSC infusion on or after January 1, 2013 and died before study data collection.	Genetic: Allo-HSCT; Allogeneic Hematopoietic Stem Cell Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of transplant-related mortality (TRM).	TRM is defined as death due to any transplantation-related cause other than disease progression.	Through 100 and 365 days post allo-HSC infusion
Incidence and timing of neutrophil engraftment.		1-48 (± 1) months post allo-HSC infusion
Incidence and timing of platelet engraftment		1-48 (± 1) months post allo-HSC infusion
Incidence of engraftment failure or allograft rejection.		1-48 (± 1) months post allo-HSC infusion
Incidence of primary donor-derived chimerism of ≥50%.		by 100 days post allo-HSC infusion
Frequency and severity of Criteria for Adverse Events (CTCAE) ≥Grade 3 AEs, CTCAE ≥Grade 3 infections, and all SAEs.		1-48 (± 1) months post allo-HSC infusion
Proportion of subjects who experience either ≥Grade II acute (Graft versus Host Disease) GVHD or chronic GVHD.		1-48 (± 1) months post allo-HSC infusion
Incidence of ≥Grade II acute GVHD.		1-48 (± 1) months post allo-HSC infusion
Incidence of chronic GVHD.		1-48 (± 1) months post allo-HSC infusion
Number of emergency room visits.		1-48 (± 1) months post allo-HSC infusion
Number and duration of intensive care unit stay.		1-48 (± 1) months post allo-HSC infusion
Number and duration of in-patient hospitalization.		1-48 (± 1) months post allo-HSC infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Major Functional Disabilities (MFDs).	MFDs is defined as any of the following: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement.	1-48 (± 2) months post allo-HSC infusion
Change from Baseline in Loes score		1-48 (± 2) months post allo-HSC infusion
Change from Baseline in Neurological Function Score (NFS)		1-48 (± 2) months post allo-HSC infusion
Frequency and timing of resolution of gadolinium enhancement on MRI, if applicable		1-48 (± 2) months post allo-HSC infusion
MFD-free survival		48 (± 2) months post allo-HSC infusion
Overall survival		48 (± 2) months post allo-HSC infusion

Collaborators and Investigators

• Sponsor: bluebird bio
• Investigators: Study Director: Elizabeth McNeil, MD MSc, bluebird bio, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): December 6, 2019
• Study Completion (Actual): December 6, 2019

Study Registration Dates

• First Submitted: July 28, 2014
• First Submitted That Met QC Criteria: July 29, 2014
• First Posted (Estimate): July 31, 2014

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 19, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: X-linked Adrenoleukodystrophy; Hematopoietic Stem Cells
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Leukoencephalopathies; Adrenal Gland Diseases; Hereditary Central Nervous System Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Adrenoleukodystrophy
• Other Study ID Numbers: ALD-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes