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A Study Evaluating the Efficacy and Safety of LentiGlobin BB305 Drug Product in Beta-Thalassemia Major and Sickle Cell Disease

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
bluebird bio Identifier:
First received: May 14, 2014
Last updated: October 17, 2016
Last verified: October 2016
This is a Phase 1/2, open label, safety, and efficacy study of the administration of LentiGlobin BB305 Drug Product to subjects with either beta-thalassemia major or severe sickle cell disease (SCD).

Condition Intervention Phase
Beta-Thalassemia Major
Sickle Cell Disease
Genetic: LentiGlobin BB305 Drug Product
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the Beta-Hemoglobinopathies (Sickle Cell Disease and Beta-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral Beta-A-T87Q Globin Vector (LentiGlobin BB305 Drug Product)

Resource links provided by NLM:

Further study details as provided by bluebird bio:

Primary Outcome Measures:
  • Success and kinetics of hematopoietic stem cell (HSC) engraftment [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: Yes ]
  • Incidence of transplant related mortality through 100 days post treatment [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: Yes ]
  • Detection of vector derived replication-competent lentivirus (RCL) in any subject [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: Yes ]
  • Characterization of events of insertional mutagenesis leading to clonal dominance or leukemia [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: Yes ]
  • Monitoring of laboratory parameters and frequency and severity of clinical AEs [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: Yes ]
    AEs assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.

Secondary Outcome Measures:
  • Quantify gene transfer efficiency and expression by evaluation [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: No ]
    Therapeutic globin expression, as measured by assessing the ratio of beta A-T87Q-globin to alpha-globin in whole blood, as well as the amount of beta A-T87Q-globin as a fraction of all beta-chains in whole blood

  • Quantify gene transfer efficiency and expression by evaluation [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: No ]
    Average vector copy number (VCN) in cell populations from peripheral blood and bone marrow containing the integrated LentiGlobin BB305 lentiviral vector.

  • Efficacy [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: No ]
    For all subjects, red blood cell (RBC) transfusion requirements (measured in milliliters [mL] per kilogram [kg]) per month and per year post transplant

  • Efficacy [ Time Frame: 1-24 months post-transplant ] [ Designated as safety issue: No ]
    For sickle cell disease (SCD) subjects only, vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) events in each subject compared with the 2 year pre-treatment period

Estimated Enrollment: 7
Study Start Date: July 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product (autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q-globin gene)
Genetic: LentiGlobin BB305 Drug Product
  • autologous CD34+ hematopoietic stem cells (HSCs) transduced with the LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene
  • Subjects with beta-thalassemia major will undergo HSC procurement by bone marrow harvest or apheresis after mobilization with filgrastim, a granulocyte-colony stimulating factor (G-CSF), alone or in combination with plerixafor, as decided by the clinical transplant team.
  • Stem cell mobilization by is contraindicated in sickle cell disease (SCD), as it could induce a sickle cell crisis; thus, procurement of HSCs for subjects with severe SCD will be conducted by bone marrow harvest.


Ages Eligible for Study:   5 Years to 35 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Be between 5 and 35 years of age, inclusive.
  2. Have severe sickle cell disease (SCD) or transfusion dependent beta-thalassemia major, regardless of the genotype with the diagnosis confirmed by Hb studies. Transfusion dependence is defined as requiring at least 100 mL/kg/year of packed red blood cells (pRBCs).
  3. Be eligible for allogeneic HSC transplant based on institutional medical guidelines, but without a matched related donor.
  4. Have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

    Subjects with severe SCD also must:

  5. Have failed to achieve adequate clinical benefit following hydroxyurea treatment with sufficient dosage, for at least 4 months unless this treatment was not indicated or not well tolerated.
  6. Have 1 or more of the following poor prognostic risk factors:

    • Recurrent vaso occlusive crises (at least 2 episodes in the preceding year or in the year prior to start of a regular transfusion program).
    • Presence of any significant cerebral abnormality on magnetic resonance imaging (MRI) (such as stenosis or occlusions).
    • Stroke without any severe cognitive disability.
    • Osteonecrosis of 2 or more joints.
    • Anti-erythrocyte alloimmunization (>2 antibodies).
    • Presence of sickle cell cardiomyopathy documented by Doppler echocardiography.
    • Acute chest syndrome (at least 2 episodes) defined by an acute event with pneumonia-like symptoms (e.g., cough, fever [>38.5°C], acute dyspnea, expectoration, chest pain, findings upon lung auscultation, tachypnea, or wheezing) and the presence of a new pulmonary infiltrate. Subjects with a chronic oxygen saturation <90% (excluding periods of SCD crisis) or carbon monoxide diffusing capacity (DLco) less than 60% in the absence of an infection should not be included in the study.

Exclusion Criteria:

  1. Availability of a willing 10 /10 matched HLA identical sibling hematopoietic cell donor, unless recommendation for enrollment is provided by the Comité de Surveillance following a review of the case.
  2. Clinically significant, active bacterial, viral, fungal, or parasitic infection.
  3. Contraindication to anesthesia for bone marrow harvesting.
  4. Any prior or current malignancy, myeloproliferative or immunodeficiency disorder.
  5. A white blood cell (WBC) count <3×10^9/L and/or platelet count <120×10^9/L.
  6. History of major organ damage including:

    • Liver disease, with transaminase levels >3× upper limit of normal.
    • This observation will not be exclusionary if a liver biopsy shows no evidence of extensive bridging fibrosis, cirrhosis, or acute hepatitis.
    • Histopathological evidence of extensive bridging fibrosis, cirrhosis, or acute hepatitis on liver biopsy.
    • Heart disease, with a left ventricular ejection fraction <25%.
    • Kidney disease with a calculated creatinine clearance <30% normal value.
    • Severe iron overload, which in the opinion of the physician is grounds for exclusion.
    • A cardiac T2* <10 ms by magnetic resonance imaging (MRI).
    • Evidence of clinically significant pulmonary hypertension requiring medical intervention.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02151526

Paris, France
Sponsors and Collaborators
bluebird bio
Study Director: Mohammed Asmal, MD, PhD bluebird bio, Inc.
  More Information

Responsible Party: bluebird bio Identifier: NCT02151526     History of Changes
Other Study ID Numbers: HGB-205  2012-000695-42 
Study First Received: May 14, 2014
Last Updated: October 17, 2016
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn processed this record on October 25, 2016