This trial is active, not recruiting.

Conditions childhood cerebral adrenoleukodystrophy, (x-linked adrenoleukodystrophy cerebral childhood)
Treatments lenti-d drug product, busulfan, cyclophosphamide, filgrastim
Phase phase 2/phase 3
Sponsor bluebird bio
Start date August 2013
End date August 2018
Trial size 17 participants
Trial identifier NCT01896102, ALD-102


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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).

Primary Outcomes

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

Secondary Outcomes

Change from Baseline in Loes score as measured by brain MRI.
time frame: 24 mon (±2 months) post-transplant
Change from Baseline in NFS.
time frame: 24 mon (± 2 months) post-transplant
Resolution of gadolinium positivity on MRI
time frame: 24 mon (± 2 months) post-transplant

Eligibility Criteria

Male participants up to 17 years old.

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.

Additional Information

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)
Principal investigator David Williams, M.D.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by bluebird bio.