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

NCT02204904 | Terminated

• 1 other identifier: ALD-103
• Study Type: observational
• Target: 59
• Locations: 7 countries
• Sites: 13

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.

Conditions

X-Linked Adrenoleukodystrophy (X-ALD); Cerebral Adrenoleukodystrophy (CALD); Adrenoleukodystrophy (ALD)

Keywords

X-linked Adrenoleukodystrophy; Hematopoietic Stem Cells

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (6)

• Incidence of Major Functional Disabilities (MFDs).

  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

Study Arms (3)

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

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

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

Interventions

Allo-HSCT GENETIC

Allogeneic Hematopoietic Stem Cell Transplantation

Allo-HSCT partial prospective/retrospective; Allo-HSCT prospective; Allo-HSCT retrospective

Eligibility Criteria

• Age: Up to 17 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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

You may qualify if:

• 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.
• 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.
• Have a confirmed diagnosis of CALD as defined by abnormal VLCFA profile and cerebral lesion on brain MRI.
• 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).

You may not qualify if:

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

Sponsors & Collaborators

• Genetix Biotherapeutics Inc.: lead

Study Sites (13)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Boston Children's Hospital/Massachusetts General Hospital

Boston, Massachusetts, 02141, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Hospital Austral

Buenos Aires, Argentina

Location

McGill University Health Centre

Montreal, Quebec, H3H 2R9, Canada

Location

University Hospital Leipzig

Leipzig, Germany

Location

IRCCS Ospedale Pediatrico Bambine Gesú

Roma, 00165, Italy

Location

Princess Maxima Center for Pediatric Oncology (PMC)

Utrecht, Netherlands

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34781360 DERIVED

MeSH Terms

Conditions

Adrenoleukodystrophy

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Elizabeth McNeil, MD MSc

  bluebird bio, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2014
• First Posted: July 31, 2014
• Study Start: April 1, 2015
• Primary Completion: December 6, 2019
• Study Completion: December 6, 2019
• Last Updated: May 21, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share

Locations

US (6); AR (1); GB (2); IT (1); CA (1); DE (1); NL (1)