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A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01896102
Recruitment Status : Active, not recruiting
First Posted : July 11, 2013
Last Update Posted : January 19, 2021
Information provided by (Responsible Party):
bluebird bio

Brief Summary:
This trial will assess the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of cerebral adrenoleukodystrophy (CALD). A participant's blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the participant following myeloablative conditioning.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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 Cerebral Adrenoleukodystrophy (CALD)
Actual Study Start Date : August 21, 2013
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Arm Intervention/treatment
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. Lenti-D Drug Product is administered by IV infusion following myeloablative conditioning with busulfan and cyclophosphamide.
Other Names:
  • elivaldogene autotemcel
  • eli-cel

Primary Outcome Measures :
  1. Percentage of Participants who are Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 [ Time Frame: Month 24 post-transplant ]
    The MFDs are loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, complete loss of voluntary movement.

  2. Percentage of Participants who Experience Either Acute (Greater than or Equal [>or=] Grade II) or Chronic Graft Versus Host Disease (GVHD) by Month 24 [ Time Frame: Month 24 post-transplant ]

Secondary Outcome Measures :
  1. Percentage of Participants Without Gadolinium Enhancement (GdE) at Month 24 [ Time Frame: Month 24 post-transplant ]
    Percentage of participants without Gadolinium Enhancement (that is [i.e.,] negative for Gadolinium Enhancement [GdE-]) on Magnetic Resonance Imaging (MRI).

  2. Time to Sustained Resolution of Gadolinium Positivity on MRI [ Time Frame: Month 24 post-transplant ]
    Sustained is defined as gadolinium resolution without a subsequent evaluation indicating gadolinium positivity.

  3. Change in total Neurologic Function Score (NFS) from Baseline to Month 24 post-transplant [ Time Frame: Baseline, Month 24 post-transplant ]
    The NFS is a 25-point score used to evaluate the severity of gross neurologic dysfunction in CALD by scoring 15 symptoms (functional domains) across 6 categories. Listed here are the 15 symptoms followed by their maximal score out of 25 points: a) Hearing / auditory processing problems-1, b) Aphasia / apraxia-1, c) Loss of communication-3, d) Vision impairment /field cut-1, e) Cortical blindness-2, f) Swallowing / other central nervous system (CNS) dysfunctions-2, g) Tube feeding-2, h) Running difficulties / hyperreflexia-1, i) Walking difficulties / spasticity / spastic gait (no assistance)-1, j) Spastic gait (needs assistance)-2, k) Wheelchair dependence-2, l) Complete loss of voluntary movement-3, m) Episodes of incontinence -1, n) Total incontinence-2, o) Nonfebrile seizures-1. A score of "0" denotes absence of clinical signs of cerebral disease. Maximal signs within a domain score the total of all grades within that domain.

  4. Major Functional Disability (MFD)-free Survival Over Time [ Time Frame: up to Month 24 (+or- 1 month) post-transplant ]
    MFD-free survival over time is defined as time from drug product infusion to either second transplant, MFD, or death due to any cause, whichever occurs first.

  5. Overall Survival [ Time Frame: up to Month 24 (+or- 1 month) post-transplant ]
  6. Percentage of Participants with Neutrophil Engraftment by 42 days Post-drug Product Infusion [ Time Frame: 42 days post-drug product infusion ]
  7. Time to Neutrophil Engraftment Post-drug Product Infusion [ Time Frame: 42 days post-drug product infusion ]
  8. Percentage of Participants with Platelet Engraftment by Month 24 [ Time Frame: Month 24 post-drug product infusion ]
  9. Time to Platelet Engraftment Post-drug Product Infusion [ Time Frame: up to Month 24 post-drug product infusion ]
  10. Percentage of Participants with Loss of Engraftment Post-drug Product Infusion by Month 24 [ Time Frame: Month 24 post-drug product infusion ]
  11. Percentage of Participants who Undergo a Subsequent Hematopoietic Stem Cell (HSC) Infusion by Month 24 [ Time Frame: Month 24 post-transplant ]
  12. Percentage of Participants with Transplant-related Mortality Through 100 and 365 days Post-drug Product Infusion [ Time Frame: Through 100 and 365 days post-drug product infusion ]
  13. Percentage of Participants with Adverse Events (AEs) in Selected Categories [ Time Frame: Month 24 post-transplant ]
    Percentage of participants with severity of clinical AEs greater than or equal to (> or =) Grade 3 AEs, all drug-product related AEs, all serious adverse events (SAEs), AEs > or = Grade 3 infections by Month 24.

  14. Percentage of Participants with Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 [ Time Frame: Month 24 post-transplant ]
    Laboratory parameters will include hematology, clinical chemistry, and liver function tests.

  15. Percentage of Participants with Greater Than or Equal to (>or=) Grade II Acute Graft Versus Host Disease (GVHD) by Month 24 [ Time Frame: Month 24 post-transplant ]
  16. Percentage of Participants with Chronic Graft Versus Host Disease (GVHD) by Month 24 [ Time Frame: Month 24 post-transplant ]
  17. Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
  18. Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
  19. Duration of in-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
  20. Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
  21. Duration of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) by Month 24 [ Time Frame: Month 24 post-transplant ]
  22. Number of Participants in which Vector-Derived Replication Competent Lentivirus (RCL) is Detected by Month 24 [ Time Frame: Month 24 post-transplant ]
  23. Number of Participants with Insertional Oncogenesis by Month 24 [ Time Frame: Month 24 post-transplant ]
    Insertional oncogenesis including Myelodysplasia, Leukemia, Lymphoma by Month 24.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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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 institutional review board (IRB)/Independent Ethics Committee (IEC) approved consent (informed assent will be sought from capable participants, 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, participant assent.
  3. Active cerebral adrenoleukodystrophy (ALD) as defined by:

    1. Elevated very long chain fatty acids (VLCFA) values, and
    2. Active CNS disease established by central radiographic review of brain magnetic resonance imaging (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. NFS less than or equal to (<or=) 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 very long chain fatty acids (VLCFA) levels. Note: participants 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 absolute neutrophil count (ANC) count < 1500 cells/ cubic milli meter (mm3),
    • Platelet count < 100,000 cells/mm3, or
    • Hemoglobin < 10 gram per deciliter (g/dL).
    • Uncorrected bleeding disorder.
  7. Hepatic compromise as evidenced by:

    • Aspartate transaminase (AST) value > 2.5×upper limit of normal (ULN)
    • Alanine transaminase (ALT) value > 2.5×ULN
    • Total bilirubin value > 3.0 milligram per deciliter (mg/dL), except if there is a diagnosis of Gilbert's Syndrome and the participant is otherwise stable
  8. Renal compromise as evidenced by abnormal renal function (actual or calculated creatinine clearance < 50 milliliter per minute [mL/min])
  9. Cardiac compromise as evidenced by left ventricular ejection fraction <40 percent (%)
  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 participants 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. Participants with past exposure to hepatitis B virus (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 participants 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 participants. Male participants 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.
  15. Any contraindications to the use of granulocyte colony stimulating (G-CSF) during the mobilization of HSCs, and any contraindications to the use of busulfan or cyclophosphamide, including known hypersensitivity to the active substances or to any of the excipients in their formulations.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01896102

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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
Medeos SRL
Buenos Aires, Argentina, C1022
Australia, South Australia
Women and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Hôpital Bicêtre
Le Kremlin-Bicêtre Cedex, France, 94275
University of Leipzig
Leipzig, Germany, 04103
United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust
London, United Kingdom, WC1N3JH
Sponsors and Collaborators
bluebird bio
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Study Director: Andrew Dietz, MD. 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
Principal Investigator: Adrian Thrasher, MD, PhD Great Ormond Street Hospital for Chidren NHS Foundation Trust
Principal Investigator: Patrick Aubourg, MD, PhD Hôpital Bicêtre
Principal Investigator: Jorn-Sven Kuhl, MD University of Leipzig
Principal Investigator: Nicholas Smith, MD Women and Children's Hospital
Principal Investigator: Hernan Amartino, MD Medeos SRL
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: bluebird bio Identifier: NCT01896102    
Other Study ID Numbers: ALD-102
2011-001953-10 ( EudraCT Number )
First Posted: July 11, 2013    Key Record Dates
Last Update Posted: January 19, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Bluebird bio is committed to transparency and appropriately de-identified patient-level datasets and supporting documents may be shared following attainment of applicable marketing approvals associated with this study and consistent with criteria established by bluebird bio and/or industry best practices to maintain the privacy of study participants. For enquiries, please contact us at

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by bluebird bio:
X-linked adrenoleukodystrophy
Gene therapy
Hematopoietic stem cell
Additional relevant MeSH terms:
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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 Insufficiency
Adrenal Gland Diseases
Endocrine System Diseases