This study will enroll subjects with transfusion dependent beta-thalassemia, 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: 20.1 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 =50 years of age at the time of consent or assent (as applicable), and able to provide written consent (adults, or legal guardians, as applicable) or assent (adolescents or children). Pediatric subjects (=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 other than beta0 (e.g., beta+, betaE, betaC) on at least one HBB allele. For the purpose of this study, the HBB mutation IVS I-110 (G -> A) will be considered equivalent to a beta0 mutation. 2. Positive for presence of HIV-1 or HIV-2, HBV, or HCV. 3. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator. 4. A white blood cell (WBC) count 92% on room air. In the presence of clinically significant abnormal findings on chest radiograph, clinically significant abnormal findings on the respiratory exam, or oxygen saturation by pulse oximetry =92% on room air, the subject will be excluded. 13. A cardiac T2* <10 ms by MRI. 14. Any other evidence of severe iron overload that, in the investigator’s opinion, 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 human leukocyte antigen (HLA)-matched family donor. Ifrequired by regional authority, patients with a known and available matched unrelated donor will be excluded from the study. 22. Any contraindications to the use of G-CSF and plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products used during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of treatment with LentiGlobin BB305 Drug Product in subjects =50 years of age with transfusion-dependent beta-thalassemia, who have a beta0/beta0, beta0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype.;Secondary Objective: To evaluate the safety of treatment with LentiGlobin BB305 Drug Product in subjects =50 years of age with transfusion-dependent beta-thalassemia, who have a beta0/beta0, beta0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype. ;Primary end point(s): EFFICACY ENDPOINT -The proportion of subjects who meet the definition of “transfusion independence” (TI). TI is defined as a weighted average Hb =9 g/dL without any pRBC transfusions for a continuous period of =12 months at any time during the study after drug product infusion.;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): EFFICACY ENDPOINTS - Characterization of subjects achieving TI - The proportion of subjects who meet the definition of transfusion reduction (TR), defined as demonstration of a =60% reduction in the annualized volume of pRBC transfusion requirements (in mL/kg) in the post-treatment time period from 12 months post-drug product infusion through Month 24 (approximately a 12-month period), compared to the annualized mL/kg pRBC transfusion requirement during the 2 years prior to study enrollment -Characterization of transfusion reduction (TR) - Weighted average nadir Hb during the 2 years prior to enrollment compared to weighted average nadir Hb from 12 months post-drug product infusion through the Month 24 Visit - Unsupported total Hb levels over time - Characterization of use of iron chelation and/or therapeutic phlebotomy among all subjects - Evaluation of the change in iron burden over time - Evaluation of health-related quality of life (HRQoL) over time PHARMACODYNAMIC ENDPOINTS - ßA-T87Q-globin expression over time - VCN in peripheral blood over time SAFETY ENDPOINTS - Success and kinetics of HSC engraftment - Incidence of transplant-related mortality through 100 days and through 365 days post-drug product infusion - Overall survival (OS) - Detection of vector-derived replication competent lentivirus (RCL) in any subject - The number of subjects with insertional oncogenesis (myelodysplasia, leukemia, lymphoma etc.) - Monitoring of laboratory parameters - Frequency and severity of clinical adverse events - Incidence of acute (=Grade 2) and/or chronic graft-versus-host disease (GVHD);Timepoint(s) of evaluation of this end point: 24 Months | — |
Countries
France, Germany, Greece, Italy, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
bluebird bio, Inc.
Outcome results
None listed