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 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|
|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|
|Los Angeles, CA||Mattel Children's Hospital UCLA/Ronald Reagan UCLA Medical Center||no longer recruiting|
|Boston, MA||Boston Children's Hospital/Massachusetts General Hospital||no longer recruiting|
|Minneapolis, MN||University of Minnesota||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
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
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
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.
|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.|
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