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

Terminated

• Conditions: X-Linked Adrenoleukodystrophy (X-ALD); Cerebral Adrenoleukodystrophy (CALD); Adrenoleukodystrophy (ALD)
• Interventions: Genetic: Allo-HSCT

• Registration Number: NCT02204904
• Lead Sponsor: bluebird bio

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-07-28
• Study First Submitted QC: 2014-07-29
• Study First Posted: 2014-07-31
• Study Start: 2015-04
• Status Verified: 2019-12
• Primary Completion: 2019-12-06
• Study Completion: 2019-12-06
• Last Update Submitted: 2020-05-19
• Last Update Posted: 2020-05-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 59

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).

Read More

Exclusion Criteria

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

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Allo-HSCT prospective	Allo-HSCT	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.
Allo-HSCT partial prospective/retrospective	Allo-HSCT	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
Allo-HSCT retrospective	Allo-HSCT	Subjects who received an allo-HSC infusion on or after January 1, 2013 and died before study data collection.

Primary Outcome Measures

Name	Time	Method
Incidence and timing of neutrophil engraftment.	1-48 (± 1) months 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
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
Incidence of transplant-related mortality (TRM).	Through 100 and 365 days post allo-HSC infusion	TRM is defined as death due to any transplantation-related cause other than disease progression.
Incidence and timing of platelet engraftment	1-48 (± 1) months post allo-HSC infusion
Incidence of primary donor-derived chimerism of ≥50%.	by 100 days post allo-HSC infusion
Number and duration of intensive care unit stay.	1-48 (± 1) months post allo-HSC infusion
Incidence of engraftment failure or allograft rejection.	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
Number of emergency room visits.	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

Name	Time	Method
MFD-free survival	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
Incidence of Major Functional Disabilities (MFDs).	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.
Overall survival	48 (± 2) months post allo-HSC infusion

Trial Locations

Locations (13)

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Great Ormond Street Hospital; 🇬🇧 London, United Kingdom

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Boston Children's Hospital/Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

IRCCS Ospedale Pediatrico Bambine Gesú; 🇮🇹 Roma, Italy

University Hospital Leipzig; 🇩🇪 Leipzig, Germany

McGill University Health Centre; 🇨🇦 Montréal, Quebec, Canada

Princess Maxima Center for Pediatric Oncology (PMC); 🇳🇱 Utrecht, Netherlands

Hospital Austral; 🇦🇷 Buenos Aires, Argentina

Central Manchester University Hospitals NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom