This study will enroll subjects with transfusion dependent beta-thalassemia, who do not have beta0/beta0 genotype, defined by a history of at least 100 mL/kg/year of packed red blood cells (pRBCs) or = 8 transfusions of pRBCs per year in the 2 years preceding enrollment. MedDRA version: 19.0 Level: LLT Classification code 10054660 Term: Thalassemia beta System Organ Class: 100000004850
Conditions
Sponsors
bluebird bio, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects between 12 and 50 years of age, inclusive 2. Diagnosis of transfusion-dependent thalassemia (including severe HbE/beta-thalassemia), also known as beta-thalassemia major, with a history of at least 100 mL/kg/year of pRBCs or = 8 transfusions of pRBCs per year for the prior 2 years 3. Clinically stable and eligible to undergo HSCT 4. Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records on RBC transfusions, in-patient hospitalization, and iron chelation history Are the trial subjects under 18? yes Number of subjects for this age range: 5 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Presence of a mutation characterized as beta0 on both HBB alleles. For the purpose of this study, the HBB mutation IVS I-110 (G -> A) will be considered equivalent to beta0 and be excluded 2. Positive for presence of HIV-1 or HIV-2, HBV, or HCV 3. Clinically significant and active bacterial, viral, fungal, or parasitic infection 4. A WBC count < 3 × 10^9/L, and/or platelet count < 100 × 10^9/L not related to hypersplenism 5. Uncorrected bleeding disorder 6. Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder 7. Immediate family member with a known Familial Cancer Syndrome 8. Prior HSCT 9. Advanced liver disease 10. Baseline estimated glomerular filtration rate < 70 mL/min/1.73 m^2 11. Uncontrolled seizure disorder 12. Diffusion capacity of carbon monoxide (DLco) < 50% of predicted 13. A cardiac T2* < 10 ms by MRI 14. Any other evidence of severe iron overload that warrants exclusion 15. Participation in another clinical study with an investigational drug within 30 days of Screening 16. Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or investigator 17. Prior receipt of gene therapy 18. Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study 19. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects 20. An assessment by the investigator that the subject would not comply with the study procedures outlined in the protocol 21. A known and available HLA-matched family donor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of treatment with LentiGlobin BB305 Drug Product in subjects =12 and =50 of age with transfusion-dependent beta-thalassemia, who do not have beta0/beta0 genotype. ;Secondary Objective: To evaluate the safety of treatment with LentiGlobin BB305 Drug Product in subjects =12 and =50 of age with transfusion-dependent beta-thalassemia, who do not have beta0/beta0 genotype. ;Primary end point(s): EFFICACY ENDPOINT - The proportion of subjects who meet the definition of “transfusion independence” (TI). ;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): EFFICACY ENDPOINTS - Characterization of subjects achieving transfusion independence - Transfusion-free survival - Characterization of transfusion reduction (TR) among subjects not achieving TI - Trend in hemoglobin pre- and post-treatment - Characterization of use of iron chelation among all subjects - Evaluation of the change in iron burden over time EXPLORATORY EFFICACY ENDPOINTS - Evaluation of health-related quality of life (HRQoL) over time - Assessment of growth and puberty parameters (age appropriate), bone density, diabetes, endocrine evaluations, and neurocognitive development (pediatric subjects < 18 years of age) - Assessment of improvement in ineffective erythropoiesis - Correlations of pre-treatment variables with response - Measures of health resource utilization PHARMACODYNAMIC ENDPOINTS - ßA-T87Q-globin expression - VCN in cell populations from peripheral blood EXPLORATORY PHARMACODYNAMIC ENDPOINT - Relationship between measures of myeloablation and pharmacodynamic and clinical outcomes SAFETY ENDPOINTS - Success and kinetics of HSC engraftment - Incidence of transplant-related mortality through 100 days post-drug product infusion - Overall survival - Detection of vector-derived replication competent lentivirus in any subject - Characterization of events of insertional mutagenesis leading to clonal dominance or leukemia - Monitoring of laboratory parameters and frequency and severity of clinical adverse events ;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
France, Germany, Greece, Italy, Thailand, United Kingdom, United States
Contacts
Public ContactClinical Trials Operations
bluebird bio, Inc.
Outcome results
None listed