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)
Phase: Phase 2/Phase 3
DFCI Protocol ID:
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.
Massachusetts General Hospital, Children's Hospital Boston, Dana-Farber Cancer Institute
David Williams, MD,
Dana-Farber Cancer Institute
- 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
- 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
i. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and ii. Gadolinium
enhancement of demyelinating lesions on MRI.
- NFS â‰¤ 1.
- 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
- Hepatic compromise as evidenced by:
i. Aspartate transaminase (AST) value > 2.5 Ã— the upper limit of normal (ULN) or, ii.
Alanine transaminase (ALT) value > 2.5 Ã— ULN or, iii. Total bilirubin value > 3.0
mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the subject is
- Renal compromise as evidenced by abnormal renal function (creatinine clearance < 50
- 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.