Trial record 3 of 24 for:    Adrenoleukodystrophy

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 currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by bluebird bio
Sponsor:
Information provided by (Responsible Party):
bluebird bio
ClinicalTrials.gov Identifier:
NCT01896102
First received: March 22, 2013
Last updated: July 18, 2014
Last verified: July 2014
  Purpose

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: 15
Study Start Date: August 2013
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

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
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 ClinicalTrials.gov identifier: NCT01896102

Contacts
Contact: Tara O'Meara 617-797-2555 clinicaltrials@bluebirdbio.com

Locations
United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Donald Kohn, MD    310-794-1964    dkohn1@mednet.ucla.edu   
Contact: Dayna Terrazas    310-825-6708    drterrazas@mednet.ucla.edu   
Principal Investigator: Donald Kohn, MD         
United States, Massachusetts
Boston Children's Hospital/Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Colleen Dansereau    617-919-7008    Colleen.Dansereau@childrens.harvard.edu   
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Paul Orchard, MD    612-626-2313    orcha001@umn.edu   
Contact: Patty Kleinke    612-273-0857    pkleink1@fairview.org   
Principal Investigator: Paul Orchard, MD         
Sponsors and Collaborators
bluebird bio
Investigators
Study Director: Asif Paker, M.D. bluebird bio, Inc.
Principal Investigator: David Williams, M.D. Children's Hospital Boston
Principal Investigator: Christine Duncan, M.D. Children's Hospital Boston
Principal Investigator: Florian Eichler, M.D. Massachusetts General Hospital
Principal Investigator: Donald Kohn, MD University of California, Los Angeles
Principal Investigator: Paul Orchard, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: bluebird bio
ClinicalTrials.gov Identifier: NCT01896102     History of Changes
Other Study ID Numbers: ALD-102
Study First Received: March 22, 2013
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Adrenoleukodystrophy
Hereditary Central Nervous System Demyelinating Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Peroxisomal Disorders
Leukoencephalopathies
Demyelinating Diseases
Mental Retardation, X-Linked
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Metabolism, Inborn Errors
Metabolic Diseases
Adrenal Insufficiency
Adrenal Gland Diseases
Endocrine System Diseases
Busulfan
Cyclophosphamide
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 28, 2014