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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 Cerebral Adrenoleukodystrophy (CALD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by bluebird bio
Information provided by (Responsible Party):
bluebird bio Identifier:
First received: March 22, 2013
Last updated: March 20, 2017
Last verified: March 2017
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 cerebral adrenoleukodystrophy (CALD). A subject's blood stem cells will be collected and modified using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification with the Lenti-D lentiviral vector, the cells will be transplanted back into the subject following myeloablative conditioning.

Condition Intervention Phase
Cerebral Adrenoleukodystrophy (CALD)
Genetic: Lenti-D Drug Product
Phase 2
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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 Cerebral Adrenoleukodystrophy (CALD)

Resource links provided by NLM:

Further study details as provided by bluebird bio:

Primary Outcome Measures:
  • The proportion of subjects who are alive and have no Major Functional Disabilities (MFDs) as determined by key measures in the Neurological Function Score (NFS). [ Time Frame: 24 months (±1 months) post-transplant ]
  • The proportion of subjects who experience either acute (≥Grade II) or chronic GVHD at Month 24. [ Time Frame: 24 months (±1 months) post-transplant ]

Secondary Outcome Measures:
  • Incidence of resolution of gadolinium positivity on MRI (i.e., GdE-). [ Time Frame: 24 months (±1 months) post-transplant ]
  • Time to resolution of gadolinium positivity on MRI (i.e., GdE-). [ Time Frame: 24 months (±1 months) post-transplant ]
  • Change in total NFS from Baseline. [ Time Frame: 24 months (±1 months) post-transplant ]
  • MFD-free survival over time [ Time Frame: 24 months (±1 months) post-transplant ]
  • Overall survival [ Time Frame: 24 months (±1 months) post-transplant ]

Estimated Enrollment: 25
Study Start Date: August 2013
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenti-D Drug Product Genetic: Lenti-D Drug Product
Lenti-D Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein, suspended in a cryopreservative solution) is administered intravenously; dose ≥ 3.0 × 10^6 CD34+ cells/kg. Lenti-D Drug Product is administered by IV infusion following myeloablative conditioning with busulfan and cyclophosphamide.


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

Inclusion Criteria:

  1. Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local 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).
  2. Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, subject assent.
  3. Active cerebral ALD as defined by:

    1. Elevated VLCFA values, and
    2. Active 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 on MRI of demyelinating lesions.

  4. Neurological Function Score (NFS) ≤ 1.

Exclusion Criteria:

  1. Receipt of an allogeneic transplant or gene therapy.
  2. Availability of a willing 10/10 HLA-matched sibling donor (excluding female heterozygotes).
  3. 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.
  4. Receipt of an investigational study drug or procedure within 3 months before Screening that might confound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study.
  5. Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
  6. Hematological compromise as evidenced by:

    • Peripheral blood ANC count < 1500 cells/mm3,
    • Platelet count < 100,000 cells/mm3, or
    • Hemoglobin < 10 g/dL.
    • Uncorrected bleeding disorder.
  7. Hepatic compromise as evidenced by:

    • Aspartate transaminase (AST) value > 2.5×ULN
    • Alanine transaminase (ALT) value > 2.5×ULN
    • Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the subject is otherwise stable
  8. Renal compromise as evidenced by abnormal renal function (actual or calculated creatinine clearance < 50 mL/min)
  9. Cardiac compromise as evidenced by left ventricular ejection fraction <40%
  10. Immediate family member with a known or suspected familial cancer syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous polyposis).
  11. Clinically significant active bacterial, viral, fungal, parasitic, or prion-associated infection
  12. Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B; hepatitis C; human T lymphotrophic virus 1 (HTLV-1). (Note that subjects who have been vaccinated against hepatitis B [hepatitis B surface antibody-positive] who are negative for other markers of prior hepatitis B infection [eg, negative for hepatitis B core antibody (Ab)] are eligible. Subjects with past exposure to HBV [HBcAb positive and/or HBeAb positive] are also eligible for the study provided they have a negative test for HBV DNA. Also note that subjects who are positive for anti-hepatitis C antibody are eligible as long as they have a negative hepatitis C viral load).
  13. Any clinically significant cardiovascular or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures.
  14. Absence of adequate contraception for fertile subjects. Male subjects and their female partners are required to use two different effective methods of contraception from Screening through at least 6 months after drug product infusion.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01896102

Contact: Tara O'Meara 617-797-2555

United States, California
Mattel Children's Hospital UCLA/Ronald Reagan UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Dayna Terrazas    310-825-6708   
Principal Investigator: Satiro N De Oliveira, MD         
United States, Massachusetts
Boston Children's Hospital/Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Colleen Dansereau    617-919-7008   
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Kim Nelson    612-273-2925   
Contact: Maggie Kumbalek    612-273-2178   
Principal Investigator: Paul Orchard, MD         
Hôpital Bicêtre Active, not recruiting
Le Kremlin-Bicêtre Cedex, France, 94275
United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust Recruiting
London, United Kingdom, WC1N3JH
Contact: Adrian Thrasher, MD, PhD         
Principal Investigator: Adrian Thrasher, MD, PhD         
Sponsors and Collaborators
bluebird bio
Study Director: Mohammed Asmal, MD., PhD. bluebird bio, Inc.
Principal Investigator: David Williams, MD Boston Children’s Hospital
Principal Investigator: Christine Duncan, MD Boston Children’s Hospital
Principal Investigator: Florian Eichler, MD Massachusetts General Hospital
Principal Investigator: Satiro de Oliveira, MD University of California, Los Angeles
Principal Investigator: Paul Orchard, MD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Adrian Thrasher, MD, PhD Great Ormond Street Hospital for Chidren NHS Foundation Trust
Principal Investigator: Patrick Aubourg, MD, PhD Hôpital Bicêtre
  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: March 20, 2017

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

Additional relevant MeSH terms:
Adrenal Insufficiency
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hereditary Central Nervous System Demyelinating Diseases
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 Gland Diseases
Endocrine System Diseases processed this record on April 28, 2017