Condition cerebral adrenoleukodystrophy (cald)
Treatment lenti-d drug product
Phase phase 2/phase 3
Sponsor bluebird bio
Start date August 2013
End date August 2019
Trial size 25 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 cerebral adrenoleukodystrophy (CALD). A subject's blood stem cells will be collected and modified using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification with the Lenti-D lentiviral vector, the cells will be transplanted back into the subject following myeloablative conditioning.

Recruiting in the following locations…

United States California, Massachusetts, and Minnesota
Other countries United Kingdom

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
lenti-d drug product
Lenti-D Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein, suspended in a cryopreservative solution) is administered intravenously; dose ≥ 3.0 × 10^6 CD34+ cells/kg. Lenti-D Drug Product is administered by IV infusion following myeloablative conditioning with busulfan and cyclophosphamide.

Primary Outcomes

The proportion of subjects who are alive and have no Major Functional Disabilities (MFDs) as determined by key measures in the Neurological Function Score (NFS).
time frame: 24 months (±1 months) post-transplant
The proportion of subjects who experience either acute (≥Grade II) or chronic GVHD at Month 24.
time frame: 24 months (±1 months) post-transplant

Secondary Outcomes

Incidence of resolution of gadolinium positivity on MRI (i.e., GdE-).
time frame: 24 months (±1 months) post-transplant
Time to resolution of gadolinium positivity on MRI (i.e., GdE-).
time frame: 24 months (±1 months) post-transplant
Change in total NFS from Baseline.
time frame: 24 months (±1 months) post-transplant
MFD-free survival over time
time frame: 24 months (±1 months) post-transplant
Overall survival
time frame: 24 months (±1 months) post-transplant

Eligibility Criteria

Male participants up to 17 years old.

Inclusion Criteria: 1. Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local 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). 2. Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, subject assent. 3. Active cerebral ALD as defined by: 1. Elevated VLCFA values, and 2. Active 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 on MRI of demyelinating lesions. 4. Neurological Function Score (NFS) ≤ 1. Exclusion Criteria: 1. Receipt of an allogeneic transplant or gene therapy. 2. Availability of a willing 10/10 HLA-matched sibling donor (excluding female heterozygotes). 3. 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. 4. Receipt of an investigational study drug or procedure within 3 months before Screening that might confound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study. 5. Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents). 6. Hematological compromise as evidenced by: - Peripheral blood ANC count < 1500 cells/mm3, - Platelet count < 100,000 cells/mm3, or - Hemoglobin < 10 g/dL. - Uncorrected bleeding disorder. 7. Hepatic compromise as evidenced by: - Aspartate transaminase (AST) value > 2.5×ULN - Alanine transaminase (ALT) value > 2.5×ULN - Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the subject is otherwise stable 8. Renal compromise as evidenced by abnormal renal function (actual or calculated creatinine clearance < 50 mL/min) 9. Cardiac compromise as evidenced by left ventricular ejection fraction <40% 10. Immediate family member with a known or suspected familial cancer syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous polyposis). 11. Clinically significant active bacterial, viral, fungal, parasitic, or prion-associated infection 12. Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B; hepatitis C; human T lymphotrophic virus 1 (HTLV-1). (Note that subjects who have been vaccinated against hepatitis B [hepatitis B surface antibody-positive] who are negative for other markers of prior hepatitis B infection [eg, negative for hepatitis B core antibody (Ab)] are eligible. Subjects with past exposure to HBV [HBcAb positive and/or HBeAb positive] are also eligible for the study provided they have a negative test for HBV DNA. Also note that subjects who are positive for anti-hepatitis C antibody are eligible as long as they have a negative hepatitis C viral load). 13. Any clinically significant cardiovascular or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures. 14. Absence of adequate contraception for fertile subjects. Male subjects and their female partners are required to use two different effective methods of contraception from Screening through at least 6 months after drug product infusion.

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 Cerebral Adrenoleukodystrophy (CALD)
Principal investigator David Williams, MD
Trial information was received from ClinicalTrials.gov and was last updated in March 2017.
Information provided to ClinicalTrials.gov by bluebird bio.