Long-term Follow-up of Participants With Cerebral Adrenoleukodystrophy Who Were Treated With Lenti-D Drug Product

NCT02698579 | Active Not Recruiting DMC FDA Drug

• 3 other identifiers: LTF-3042024-513904-33-002015-002805-13
• Study Type: observational
• Target: 64
• Locations: 9 countries
• Sites: 13

Brief Summary

This is a multi-center, long-term safety and efficacy follow-up study for participants with cerebral adrenoleukodystrophy (CALD) who have received Lenti-D Drug Product (eli-cel) in a parent clinical study (Study ALD-102 or Study ALD-104). After completing a parent clinical study (approximately 2 years), eligible participants will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in this study.

Conditions

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

Keywords

Adrenoleukodystrophy; X-linked Adrenoleukodystrophy; Hematopoietic Stem Cells

Outcome Measures

Primary Outcomes (6)

• Major functional disability (MFD)-free survival

  The MFDs are loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, complete loss of voluntary movement.

  15 years post-drug-product infusion

• Number of participants with malignancies

  15 years post-drug-product infusion

• Number of participants who experience graft versus host disease (GVHD)

  15 years post-drug-product infusion

• Number of participants with immune-related adverse events (AEs)

  15 years post-drug-product infusion

• Number of participants with new or worsening hematologic disorders

  15 years post-drug-product infusion

• Number of participants with new or worsening neurologic disorders

  15 years post-drug-product infusion

Secondary Outcomes (3)

• Number of participants who undergo subsequent stem cell transplantation

  15 years post-drug-product infusion

• Change from baseline in neurological function score (NFS)

  15 years post-drug-product infusion

• Number of participants without gadolinium enhancement (GdE) status on magnetic resonance imaging (MRI)

  15 years post-drug-product infusion

Study Arms (1)

Long-term followup

Participants who have received Lenti-D Drug Product in a parent clinical study (bluebird bio-sponsored clinical studies ALD-102 and ALD-104) and who meet the eligibility criteria for the Study LTF-304 will be followed in this long-term followup study for 13 years (for a total of 15 years of follow-up after drug product infusion in the parent studies).

Genetic: No interventional drug product utilized in this follow-up study

Interventions

No interventional drug product utilized in this follow-up study GENETIC

Participants received a single IV infusion of Lenti-D Drug Product (also known as elivaldogene autotemcel or eli-cel) in either parent Study ALD-102 or ALD-104. The objectives of this long-term follow-up study are to assess long-term safety and efficacy following completion of participation in parent studies. Vector copy number (VCN) measurement, safety evaluations, disease-specific assessments, and assessments to monitor for long-term complications of autologous transplant are conducted in this study.

Long-term followup

Eligibility Criteria

• Age: Up to 19 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants with cerebral adrenoleukodystrophy (CALD) who have received Lenti-D Drug Product in a parent clinical study will be expected to participate in this long-term follow-up study.

You may qualify if:

• Provision of written informed consent for this study by the participant or participant's parent(s)/ legal guardian(s) and written informed assent by participant, if applicable
• Have received eli-cel in a parent clinical study

Sponsors & Collaborators

• Genetix Biotherapeutics Inc.: lead

Study Sites (13)

Mattel Children's Hospital-UCLA

Los Angeles, California, 90095, United States

Location

Lucile Packard Children's Hospital - Stanford

Palo Alto, California, 94304, United States

Location

Boston Children's Hospital/Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Instituto Neurogenia

Caba, Argentina

Location

Women's and Children's Hospital

North Adelaide, Australia

Location

Hospital das Clínicas da Universidade de São Paulo

São Paulo, 05403-000, Brazil

Location

Hôpital Bicêtre

Le Kremlin-Bicêtre, Cedex, 94275, France

Location

Universitätsklinikum Leipzig AöR

Leipzig, 04103, Germany

Location

Ospedale Pediatrico Bambino Gesù

Rome, 00165, Italy

Location

Prinses Maxima Center

Utrecht, 3584, Netherlands

Location

Royal Free London Hospital

London, England, NW3 2QG, United Kingdom

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Related Publications (2)

• Eichler F, Duncan CN, Musolino PL, Lund TC, Gupta AO, De Oliveira S, Thrasher AJ, Aubourg P, Kuhl JS, Loes DJ, Amartino H, Smith N, Folloni Fernandes J, Sevin C, Sankar R, Hussain SA, Gissen P, Dalle JH, Platzbecker U, Downey GF, McNeil E, Demopoulos L, Dietz AC, Thakar HL, Orchard PJ, Williams DA. Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2024 Oct 10;391(14):1302-1312. doi: 10.1056/NEJMoa2400442.

  PMID: 39383459 DERIVED

• Duncan CN, Bledsoe JR, Grzywacz B, Beckman A, Bonner M, Eichler FS, Kuhl JS, Harris MH, Slauson S, Colvin RA, Prasad VK, Downey GF, Pierciey FJ, Kinney MA, Foos M, Lodaya A, Floro N, Parsons G, Dietz AC, Gupta AO, Orchard PJ, Thakar HL, Williams DA. Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2024 Oct 10;391(14):1287-1301. doi: 10.1056/NEJMoa2405541.

  PMID: 39383458 DERIVED

Related Links

• Parent Study ALD-102 protocol registrations and summary result disclosure
• Parent Study ALD-104 protocol registrations and summary result disclosure

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

• Vinod K Prasad, MD, FRCP

  bluebird bio, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2016
• First Posted: March 3, 2016
• Study Start: January 22, 2016
• Primary Completion (Estimated): August 1, 2038
• Study Completion (Estimated): August 1, 2038
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

BR (1); IT (1); GB (2); US (4); NL (1); AU (1); FR (1); AR (1); DE (1)