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

• ClinicalTrials.gov Identifier: NCT02204904
• Recruitment Status: Recruiting
• First Posted: July 31, 2014
• Last Update Posted: July 19, 2019
• Sponsor: bluebird bio
• Information provided by (Responsible Party): bluebird bio

Study Description

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.

Condition or disease	Intervention/treatment
X-Linked Adrenoleukodystrophy (X-ALD); Cerebral Adrenoleukodystrophy (CALD); Adrenoleukodystrophy (ALD)	Genetic: Allo-HSCT

Study Design

• Study Type: Observational
• Estimated Enrollment: 60 participants
• Observational Model: Cohort
• Time Perspective: Other
• 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
• Actual Study Start Date: April 2015
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: May 2021

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Incidence of Major Functional Disabilities (MFDs). [ Time Frame: 1-48 (± 2) months post allo-HSC infusion ]
   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.
2. Change from Baseline in Loes score [ Time Frame: 1-48 (± 2) months post allo-HSC infusion ]
3. Change from Baseline in Neurological Function Score (NFS) [ Time Frame: 1-48 (± 2) months post allo-HSC infusion ]
4. Frequency and timing of resolution of gadolinium enhancement on MRI, if applicable [ Time Frame: 1-48 (± 2) months post allo-HSC infusion ]
5. MFD-free survival [ Time Frame: 48 (± 2) months post allo-HSC infusion ]
6. Overall survival [ Time Frame: 48 (± 2) months post allo-HSC infusion ]

Eligibility Criteria

• Ages Eligible for Study: up to 17 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• 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

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.

Contacts and Locations

Contacts

Contact: bluebird bio; 339-499-9300; clinicaltrials@bluebirdbio.com

Locations

United States, California

Children's Hospital Los Angeles; Recruiting

Los Angeles, California, United States, 90027

Principal Investigator: Neena Kapoor, MD

Stanford University; Recruiting

Palo Alto, California, United States, 94304

Principal Investigator: Ami Shah, MD

United States, Massachusetts

Boston Children's Hospital/Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02141

Principal Investigator: Christine Duncan, MD

Principal Investigator: Florian S Eichler, MD

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Principal Investigator: Paul Orchard, MD

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27705

Principal Investigator: Vinod Prasad, MD

United States, Pennsylvania

The Children's Hospital of Philadelphia; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Nancy Bunin, MD

Principal Investigator: Nancy Bunin, MD

United States, Utah

University of Utah School of Medicine; Withdrawn

Salt Lake City, Utah, United States, 84108

Argentina

Hospital Austral; Recruiting

Buenos Aires, Argentina

Principal Investigator: Hernan Amartino, MD

Canada, Quebec

McGill University Health Centre; Recruiting

Montréal, Quebec, Canada, H3H 2R9

Contact: Genevieve Bernard, MD

Principal Investigator: Genevieve Bernard, MD

Germany

University Hospital Leipzig; Recruiting

Leipzig, Germany

Principal Investigator: Jörn-Sven Kühl , MD

Italy

IRCCS Ospedale Pediatrico Bambine Gesú; Recruiting

Roma, Italy, 00165

Contact: Francesco Locatelli, MD

Principal Investigator: Francesco Locatelli, MD

Netherlands

Princess Maxima Center for Pediatric Oncology (PMC); Recruiting

Utrecht, Netherlands

Principal Investigator: Caroline Lindemans, MD

United Kingdom

Great Ormond Street Hospital; Recruiting

London, United Kingdom

Principal Investigator: Robert Chiesa, MD

Central Manchester University Hospitals NHS Foundation Trust; Recruiting

Manchester, United Kingdom, M13 9WL

Principal Investigator: Simon Jones, MD

Sponsors and Collaborators

bluebird bio

Investigators

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

More Information

• Responsible Party: bluebird bio
• ClinicalTrials.gov Identifier: NCT02204904 History of Changes
• Other Study ID Numbers: ALD-103
• First Posted: July 31, 2014
• Last Update Posted: July 19, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by bluebird bio:

X-linked Adrenoleukodystrophy; Hematopoietic Stem Cells

Additional relevant MeSH terms:

Adrenoleukodystrophy; 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; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Allopurinol; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Free Radical Scavengers; Antioxidants