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A Phase 2/3 Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Childhood Cerebral Adrenoleukodystrophy (CCALD)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
bluebird bio Identifier:
First received: March 22, 2013
Last updated: August 11, 2015
Last verified: June 2015
This trial will assess the efficacy and safety of autologous CD34+ hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of childhood cerebral adrenoleukodystrophy (CCALD). A subject's blood stem cells will be collected and modified using the Lenti-D lentiviral vector to add a functional copy of the human ABCD1 (ATP-binding cassette, sub-family D, member 1) complementary DNA (cDNA). After modification with the Lenti-D lentiviral vector, the cells will be transplanted back into the subject following myeloablative conditioning.

Condition Intervention Phase
Childhood Cerebral Adrenoleukodystrophy
(X-linked Adrenoleukodystrophy Cerebral Childhood)
Genetic: Lenti-D Drug Product
Drug: Busulfan
Drug: Cyclophosphamide
Drug: Filgrastim
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2/3 Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Childhood Cerebral Adrenoleukodystrophy (CCALD)

Resource links provided by NLM:

Further study details as provided by bluebird bio:

Primary Outcome Measures:
  • Assessment of the proportion of subjects who have no Major Functional Disabilities (MFDs) as determined by key measures in the Neurological Function Score (NFS). [ Time Frame: 24 months (±2 months) post-transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Loes score as measured by brain MRI. [ Time Frame: 24 mon (±2 months) post-transplant ] [ Designated as safety issue: No ]
  • Change from Baseline in NFS. [ Time Frame: 24 mon (± 2 months) post-transplant ] [ Designated as safety issue: No ]
  • Resolution of gadolinium positivity on MRI [ Time Frame: 24 mon (± 2 months) post-transplant ] [ Designated as safety issue: No ]
    Proportion of subjects who demonstrate resolution of gadolinium positivity on MRI (i.e., who are gadolinium negative) at 24 months (± 2 months) post-transplant.

Estimated Enrollment: 17
Study Start Date: August 2013
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenti-D Drug Product Genetic: Lenti-D Drug Product
Autologous CD34+ hematopoietic stem cells (HSCs) transduced with the lentiviral vector Lenti-D encoding the human ATP-binding cassette, sub-family D, member 1 (ABCD1) cDNA suspended in CryoStor® CS5 (BioLife® Solutions) cryopreservative solution containing 5% dimethyl sulfoxide (DMSO).
Drug: Busulfan Drug: Cyclophosphamide Drug: Filgrastim


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

Inclusion Criteria:

  • Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved consent. (Informed assent will be sought from capable subjects, in accordance with the directive of the IRB/IEC and with local requirements).
  • Boys aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, subject assent.
  • Active cerebral ALD as defined by: Elevated VLCFA levels, and active central nervous system (CNS) disease established by central radiographic review of brain MRI demonstrating:

    i. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and ii. Gadolinium enhancement of demyelinating lesions on MRI.

  • NFS ≤ 1.

Exclusion Criteria:

  • Receipt of an allogeneic transplant or gene therapy.
  • Availability of a willing 10/10 human leukocyte antigen (HLA)-matched sibling donor.
  • Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA levels. Note: subjects must discontinue use of these medications at time of consent.
  • Receipt of an investigational study drug or procedure within 3 months before Day -60 that might confound study outcomes.
  • Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
  • Hematological compromise as evidenced by:

    i. Peripheral blood absolute neutrophil count (ANC) < 1500 cells/mm^3 or, ii. Platelet count < 100,000 cells/mm^3 or, iii. Hemoglobin < 10 g/dL or, iv. Uncorrected bleeding disorder.

  • Hepatic compromise as evidenced by:

    i. Aspartate transaminase (AST) value > 2.5 × the upper limit of normal (ULN) or, ii. Alanine transaminase (ALT) value > 2.5 × ULN or, iii. Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the subject is otherwise stable.

  • Renal compromise as evidenced by abnormal renal function (creatinine clearance < 50 mL/min).
  • Cardiac compromise as evidenced by left ventricular ejection fraction < 40%.
  • Immediate family member with a known or suspected Familial Cancer Syndrome.
  • Clinically significant active bacterial, viral, fungal, or parasitic infection.
  • Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1, HIV 2), hepatitis B, hepatitis C, or human T lymphotrophic virus 1 (HTLV 1).
  • Any clinically significant cardiovascular or pulmonary, or other disease or condition that would be contraindicated for any of the other study procedures.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01896102

United States, California
Mattel Children's Hospital UCLA/Ronald Reagan UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Massachusetts
Boston Children's Hospital/Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
bluebird bio
Study Director: Asif Paker, M.D. bluebird bio, Inc.
Principal Investigator: David Williams, M.D. Boston Children’s Hospital
Principal Investigator: Christine Duncan, M.D. Boston Children’s Hospital
Principal Investigator: Florian Eichler, M.D. Massachusetts General Hospital
Principal Investigator: Ami J Shah, MD University of California, Los Angeles
Principal Investigator: Paul Orchard, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

Responsible Party: bluebird bio Identifier: NCT01896102     History of Changes
Other Study ID Numbers: ALD-102 
Study First Received: March 22, 2013
Last Updated: August 11, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by bluebird bio:
X-linked adrenoleukodystrophy
Gene therapy
Hematopoietic stem cell

Additional relevant MeSH terms:
Mental Retardation, X-Linked
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hereditary Central Nervous System Demyelinating Diseases
Demyelinating Diseases
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
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents processed this record on December 08, 2016