A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in β-Thalassemia Major Participants

Bluebird Bio

Status and phase

Completed

Phase 2

Phase 1

Conditions

β-thalassemia Major

Treatments

Genetic: LentiGlobin BB305 Drug Product

Study type

Interventional

Funder types

Industry

Identifiers

NCT01745120

HGB-204

Details and patient eligibility

About

This is a non-randomized, open label, multi-site, single-dose, phase 1/2 study in up to 18 participants (including at least 3 adolescents between 12 and 17 years of age, inclusive) with β-thalassemia major. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product [autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene].

Full description

Subject participation for this study will be 2 years. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 13 years post-transplant.

Enrollment

19 patients

Sex

All

Ages

12 to 35 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Participants between 12 and 35 years of age, inclusive, at the time of consent/assent, and able to provide written consent/assent, if applicable.
Diagnosis of β-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years.
Eligible for allogeneic bone marrow transplant.
Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Exclusion criteria

Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).
A white blood cell (WBC) count <3 × 10^9/L, and / or platelet count <100 × 10^9/L if not due to hypersplenism.
Uncorrected bleeding disorder.
Any prior or current malignancy or myeloproliferative or immunodeficiency disorder.
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).
Receipt of an allogeneic transplant.
Advanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.
Kidney disease with a calculated creatinine clearance <30% normal value.
Uncontrolled seizure disorder.
Diffusion capacity of carbon monoxide (DLco) <50% of predicted (corrected for hemoglobin).
A cardiac T2* <10 ms by magnetic resonance imaging (MRI).
Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion.
Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
Participation in another clinical study with an investigational drug within 30 days of Screening.
Any prior or current malignancy or myeloproliferative disorder.
Prior receipt of gene therapy.