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A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Subjects With Transfusion-Dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype

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ClinicalTrials.gov Identifier: NCT02906202
Recruitment Status : Recruiting
First Posted : September 20, 2016
Last Update Posted : February 28, 2018
Sponsor:
Information provided by (Responsible Party):
bluebird bio

Brief Summary:
This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 23 subjects ≤50 years of age with transfusion-dependent β-thalassemia (TDT), also known as β-thalassemia major, who do not have a β0 mutation at both alleles of the hemoglobin β (HBB) gene. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.

Condition or disease Intervention/treatment Phase
Beta-Thalassemia Genetic: LentiGlobin BB305 Drug Product Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype, by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age
Study Start Date : July 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020


Arm Intervention/treatment
Experimental: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product (autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene)
Genetic: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.



Primary Outcome Measures :
  1. The proportion of treated subjects who meet the definition of "transfusion independence" (TI). [ Time Frame: 12 - 24 months post-transplant ]
    TI is defined as a weighted average Hb ≥9g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after drug product infusion.


Secondary Outcome Measures :
  1. Engraftment defined as an absolute neutrophil count ≥500 cells/µL for 3 consecutive days [ Time Frame: 24 months post-transplant ]
  2. Detection of vector-derived replication competent lentivirus (RCL) using a RCL screening assay [ Time Frame: 24 months post-transplant ]
  3. Frequency of events of insertional mutagenesis leading to clonal dominance or leukemia [ Time Frame: 24 months post-transplant ]
  4. Frequency of clinical adverse events [ Time Frame: 24 months post-transplant ]
  5. Percentage of subjects with a reduction in the mL/kg RBC transfused from Month 12 through Month 24 after drug product infusion of at least 50% compared to the average annual RBC transfusion requirement during the 2 years prior to enrollment. [ Time Frame: 24 months post-transplant ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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). Provided that the DMC has approved enrolling subjects younger than 5 years of age, subjects younger than 5 years of age may be enrolled if they weigh a minimum of 6 kg and are reasonably anticipated to be able to provide at least the minimum number of cells required to initiate the manufacturing process.
  • Diagnosis of TDT with a history of at least 100 mL/kg/year of packed red blood cells (pRBCs) in the 2 years preceding enrollment (all subjects), or be managed under standard thalassemia guidelines with ≥8 transfusions of pRBCs per year in the 2 years preceding enrollment (subjects ≥12 years).
  • Clinically stable and eligible to undergo hematopoietic stem cell therapy (HSCT).
  • Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Exclusion Criteria:

  • Presence of a mutation characterized as β0 mutation at both alleles of the HBB gene.
  • Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B virus (HBV), or hepatitis C (HCV).
  • A white blood cell (WBC) count <3×10^9/L, and/or platelet count <100×10^9/L not related to hypersplenism.
  • Uncorrected bleeding disorder.
  • Any prior or current malignancy.
  • Immediate family member with a known Familial Cancer Syndrome.
  • Prior HSCT.
  • Advanced liver disease.
  • 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.
  • Participation in another clinical study with an investigational drug within 30 days of Screening.
  • Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or investigator.
  • Prior receipt of gene therapy.
  • Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects.
  • A known and available HLA-matched family donor.
  • 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 required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02906202


Contacts
Contact: bluebird bio 1 (339)499-9300 clinicaltrials@bluebirdbio.com

Locations
United States, California
Recruiting
Oakland, California, United States
United States, Illinois
Recruiting
Chicago, Illinois, United States
United States, Pennsylvania
Recruiting
Philadelphia, Pennsylvania, United States
France
Not yet recruiting
Marseille, France
Germany
Recruiting
Hannover, Germany
Greece
Not yet recruiting
Thessaloniki, Greece
Italy
Recruiting
Rome, Italy
Thailand
Recruiting
Bangkok, Thailand
United Kingdom
Recruiting
London, United Kingdom
Sponsors and Collaborators
bluebird bio
Investigators
Study Director: Mohammed Asmal bluebird bio

Responsible Party: bluebird bio
ClinicalTrials.gov Identifier: NCT02906202     History of Changes
Other Study ID Numbers: HGB-207
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn