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: Active, not recruiting
• Trial end date: 0000-00-00
• Target enrollment: 17
• Participant gender: Male

Summary

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: bluebird bio
• Treatments: Busulfan; Cyclophosphamide
• Last Updated: 2015-08-11

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.