This trial is active, not recruiting.

Condition beta-thalassemia major
Treatment lentiglobin® bb305 drug product
Phase phase 1/phase 2
Sponsor bluebird bio
Start date August 2013
End date March 2018
Trial size 18 participants
Trial identifier NCT01745120, HGB-204


This is a non-randomized, open label, multi-site, single-dose, Phase 1/2 study in up to 18 subjects (including at least 3 adolescents between 12 and 17 years of age, inclusive) with beta-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 β-A(T87Q)-globin gene].

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
lentiglobin® bb305 drug product
Transplant of autologous hematopoietic stem cells transduced with LentiGlobin® BB305 lentiviral vector.

Primary Outcomes

Evaluate the efficacy of treatment with LentiGlobin® BB305 Drug Product in subjects with β-thalassemia major as measured by the production of hemoglobin containing the therapeutic globin protein [β-A(T87Q)-globin]
time frame: 18 - 24 months post-transplant
Evaluate the safety of treatment with LentiGlobin® BB305 Drug Product in subjects with β-thalassemia major as measured by the incidence of adverse events
time frame: 0-24 months post-transplant

Secondary Outcomes

Hematopoietic stem cell engraftment
time frame: 42 days post-transplant
Assess transgene marking as determined by measurement of the average vector copy number in peripheral blood and bone marrow
time frame: 0 - 24 months post-transplant

Eligibility Criteria

Male or female participants from 12 years up to 35 years old.

Inclusion criteria: - Subjects 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 × 109/L, and / or platelet count <100 × 109/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.

Additional Information

Official title A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With β-Thalassemia Major by Transplantation of Autologous CD34+ Cells Transduced Ex Vivo With a Lentiviral β-A(T87Q)-Globin Vector (LentiGlobin® BB305 Drug Product)
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by bluebird bio.
Location data was received from the National Cancer Institute and was last updated in May 2016.