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

Study Overview
=================
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.

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

Conditions
-----------------
Cerebral Adrenoleukodystrophy (CALD), Adrenoleukodystrophy (ALD), X-Linked Adrenoleukodystrophy (X-ALD)

Intervention / Treatment
-----------------
* Genetic: Allo-HSCT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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). Exclusion Criteria: Previous treatment with a gene therapy product. Receipt of an experimental transplantation procedure.

Ages Eligible for Study
-----------------
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Allo-HSCT prospective<br>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<br>* Allogeneic Hematopoietic Stem Cell Transplantation<br>|
| Allo-HSCT partial prospective/retrospective<br>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<br>* Allogeneic Hematopoietic Stem Cell Transplantation<br>|
| Allo-HSCT retrospective<br>Subjects who received an allo-HSC infusion on or after January 1, 2013 and died before study data collection. | Genetic: Allo-HSCT<br>* Allogeneic Hematopoietic Stem Cell Transplantation<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
X-linked Adrenoleukodystrophy, Hematopoietic Stem Cells