A Phase 3 Study of Lenti-D Drug Product After Myeloablative Conditioning Using Busulfan and Fludarabine in Subjects <=17 Years of Age With Cerebral Adrenoleukodystrophy (CALD)
- Conditions
- CALDcerebral adrenoleukodystrophy10029299
- Registration Number
- NL-OMON54719
- Lead Sponsor
- bluebird bio Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
1. 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.,
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:,
a. Elevated very long chain fatty acids (VLCFA) values, and
b. Active central nervous system (CNS) disease established by central
radiographic review of brain magnetic resonance imaging (MRI) demonstrating
i. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and
ii. Gadolinium enhancement (GdE) on MRI of demyelinating lesions.,
4. Neurologic Function Score (NFS) <=1.
1. Prior receipt of an allogeneic transplant or gene therapy.,
2. Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA
levels.,
3. 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.,
4. Any conditions that make it impossible to perform MRI studies (including
allergies to anesthetics or contrast agents).,
5. Hematological compromise as evidenced by:,
a. Peripheral blood absolute neutrophil count (ANC) count <1500 cells/mm3, and
either
b. Platelet count <100,000 cells/mm3, or
c. Hemoglobin <10 g/dL.
6. Hepatic compromise as evidenced by:,
a. Aspartate transaminase (AST) value >2.5 × upper limit of normal (ULN),
b. Alanine transaminase (ALT) value >2.5 × ULN,
c. Total bilirubin value >3.0 mg/dL, except if there is a diagnosis of
Gilbert's Syndrome and the subject is otherwise stable.,
7. Baseline estimated glomerular filtration rate <70 mL/min/1.73 m2.,
8. Cardiac compromise as evidenced by left ventricular ejection fraction <40%.,
9. Immediate family member with a known or suspected Familial Cancer Syndrome.,
10. Clinically significant uncontrolled, active bacterial, viral, fungal,
parasitic, or prion associated infection.,
11. Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2);
hepatitis B virus (HBV); hepatitis C virus (HCV); human T lymphotrophic virus 1
(HTLV-1). (Note that subjects who have been vaccinated against HBV [positive
for HBV surface antibodies] who are negative for other markers of prior HBV
infection [e.g., negative for HBVhepatitis B core antibody {HBVc Ab]}] are
eligible. Subjects with past exposure to HBV [HBcAb [HBc antibodies {Ab}
positive and/or hepatitis B e-antigen antibody {HBeAb}-positive] are also
eligible for the study provided they have a negative test for HBV
deoxyribonucleic acid [DNA.]. Also note that subjects who are positive for
anti-hepatitis C Ab are eligible as long as they have a negative hepatitis C
viral load).
12. Any clinically significant cardiovascular, haematological or pulmonary
disease, or
other disease or condition that would be contraindicated for any of the
other study procedures.
13. 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 eli-cel infusion.
If subjects are truly sexually abstinent (where true sexual abstinence is
defined as being in line with the preferred and usual lifestyle of the
subject), no second method is required.
14. Any contraindications to the use of G-CSF or plerixafor during the
mobilization of hematopoietic stem cells (HSCs), and any contraindications to
the use of busulfan or fludarabine, including known hypersensitivity to the
active substances or to any of the excipients in their formulations.
15. known hypersensitivity to protamine sulphate
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the proportion of patients who are alive and have none<br /><br>of the 6 major functional disabilities at Month 24 (as per protocol).</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary endpoints include the proportion of patients without gadolinium<br /><br>enhancement at Month 24, value and change in neurological function, MFD-free<br /><br>survival over time, overall survival and Detectable vector copy number in<br /><br>peripheral blood cells by Month 6 (as per protocol).</p><br>