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)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Cerebral Adrenoleukodystrophy (CALD)
- Sponsor
- bluebird bio
- Enrollment
- 32
- Locations
- 8
- Primary Endpoint
- Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 and Without Allo-HSCT or Rescue Cell Administration
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This trial assessed the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector (also called elivaldogene autotemcel or eli-cel), for the treatment of cerebral adrenoleukodystrophy (CALD). A participant's blood stem cells were collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells were transplanted back into the participant following myeloablative conditioning. Participants in this study will be continuously followed in study LTF-304.
Detailed Description
For study ALD-102 the Transplant Population (TP), Neutrophil Engraftment Population (NEP), and Intent-to-Treat Population (ITT) were identical.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Informed consent was 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 participants, in accordance with the directive of the IRB/IEC and with local requirements).
- •Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent.
- •Active cerebral adrenoleukodystrophy (ALD) as defined by:
- •Elevated very long chain fatty acids (VLCFA) values, and
- •Active CNS disease established by central radiographic review of brain magnetic resonance imaging (MRI) demonstrating:
- •Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and
- •Gadolinium enhancement on MRI of demyelinating lesions.
- •NFS less than or equal to (\<or=) 1.
Exclusion Criteria
- •Receipt of an allogeneic transplant or gene therapy.
- •Availability of a willing 10/10 HLA-matched sibling donor (excluding female heterozygotes).
- •Use of statins, Lorenzo's Oil, or dietary regimens used to lower very long chain fatty acids (VLCFA) levels. Note: participants must discontinue use of these medications at time of consent.
- •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.
- •Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
- •Hematological compromise as evidenced by:
- •Peripheral blood absolute neutrophil count (ANC) count \< 1500 cells/ cubic milli meter (mm3),
- •Platelet count \< 100,000 cells/mm3, or
- •Hemoglobin \< 10 gram per deciliter (g/dL).
- •Uncorrected bleeding disorder.
Outcomes
Primary Outcomes
Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 and Without Allo-HSCT or Rescue Cell Administration
Time Frame: At Month 24
The 6 MFDs consisted of loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, complete loss of voluntary movement. Month 24 MFD-Free survival criteria was defined as: alive at 24 months post-infusion; had not developed any of the MFDs by 24 months post-infusion; had not received rescue cell administration or allo-HSCT by 24 months post-infusion; and had not withdrawn from the study or had not been lost to follow-up by 24 months post-infusion. Percentage of participants who were alive and have none of the 6 major functional disabilities (MFDs) at Month 24 were reported.
Proportion of Participants Who Had Experienced Either Acute ([>or=] Grade II) or Chronic Graft Versus Host Disease (GVHD) by Month 24
Time Frame: By Month 24
Acute GVHD graded on the Acute GVHD Grading Scale (I-IV): Grade I is characterized as mild disease, Grade II as moderate, Grade III as severe (involvement of any organ system), and Grade IV as life-threatening; chronic GVHD was determined by the Investigator. Percentage of participants who experienced with either acute (\>= Grade II) or chronic GVHD at Month 24 were reported.
Secondary Outcomes
- Major Functional Disability (MFD)-Free Survival Rate(At 24 months after Lenti-D drug infusion)
- Percentage of Participants Who Demonstrated Resolution of Gadolinium Positivity on Magnetic Resonance Imaging (MRI) at Month 24(At Month 24)
- Time to Sustained Resolution of Gadolinium Positivity on MRI(Up to Month 24)
- Number of Participants With Change in Total Neurologic Function Score (NFS) From Baseline up to Month 24(Baseline up to Month 24)
- Proportion of Participants With Neutrophil Engraftment by 42 Days Post-drug Product Infusion(By 42 days post-drug infusion)
- Time to Neutrophil Engraftment Post-drug Product Infusion(By 42 days post-drug infusion)
- Number of Emergency Room Visits (Post-Neutrophil Engraftment) By Month 24(From Post-Neutrophil Engraftment up to Month 24)
- Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) By Month 24(From post-neutrophil engraftment up to Month 24)
- Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) By Month 24(From post-neutrophil engraftment up to Month 24)
- Number of Participants With Vector-Derived Replication Competent Lentivirus (RCL) Detected by Month 24(By Month 24)
- Overall Survival Rate(At 24 months after Lenti-D drug infusion)
- Proportion of Participants With Engraftment Failure By Month 24(By Month 24)
- Duration of ICU Stays (Post-neutrophil Engraftment) By Month 24(From post-neutrophil engraftment up to Month 24)
- Number of Participants With Insertional Oncogenesis By Month 24(By Month 24)
- Proportion of Participants With Platelet Engraftment by Month 24(By Month 24)
- Time to Platelet Engraftment Post-drug Product Infusion(By Month 24)
- Proportion of Participants Who Underwent a Subsequent Allo-Hematopoietic Stem Cell (HSC) Infusion by Month 24(By Month 24)
- Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24(From time of drug product infusion up to Month 24)
- Percentage of Participants With Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion(From time of drug product infusion through 100 and 365 days post-drug product infusion)
- Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs(From date of informed consent up to Month 24)
- Duration of In-patient Hospitalizations (Post-Neutrophil Engraftment) up to Month 24(From post-neutrophil engraftment up to Month 24)