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)

Status: Recruiting
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.

Conducting Institutions:

Massachusetts General Hospital, Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

David Williams, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:


Children's Hospital Boston: Colleen Dansereau, Colleen.dansereau@childrens.harvard.edu

Eligibility 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

  -  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 ≤ 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

  -  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.

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