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A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in Severe Sickle Cell Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by bluebird bio
Sponsor:
Information provided by (Responsible Party):
bluebird bio
ClinicalTrials.gov Identifier:
NCT02140554
First received: May 14, 2014
Last updated: March 1, 2017
Last verified: February 2017
  Purpose
This is a non-randomized, open label, multi-site, single-dose, Phase 1 study in up to 29 adults with severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of the LentiGlobin BB305 Drug Product [consisting of autologous CD34+ hematopoietic stem cells (HSC) transduced with LentiGlobin BB305 lentiviral vector encoding the human beta A-T87Q-globin gene].

Condition Intervention Phase
Sickle Cell Disease
Genetic: LentiGlobin BB305 Drug Product
Biological: Plerixafor
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With the LentiGlobin BB305 Lentiviral Vector in Subjects With Severe Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by bluebird bio:

Primary Outcome Measures:
  • Safety [ Time Frame: 1-24 months post-transplant ]

    Safety will be evaluated by the following:

    • success and kinetics of hematopoietic stem cell (HSC) engraftment
    • safety and tolerability of plerixafor for mobilization
    • incidence of treatment-related mortality
    • incidence of mortality through 2 years after drug product infusion
    • detection of vector-derived replication competent lentivirus (RCL) in any subject
    • characterization of events of insertional mutagenesis leading to malignancy
    • monitoring of laboratory parameters and frequency and severity of clinical AEs, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03


Secondary Outcome Measures:
  • Clinical efficacy will be evaluated by comparing the frequency of clinical events secondary to sickle cell disease [ Time Frame: 1-24 months post-transplant ]

    Efficacy will be evaluated by the following:

    • severe vaso-occlusive crisis (VOC). A severe VOC is defined as an episode of pain lasting more than 2 hours severe enough to require care at a medical facility. Priapism that lasts more than 2 hours and requires care at a medical facility is considered a severe VOC
    • acute chest syndrome events, defined as an acute event with pneumonia-like symptoms and the presence of a new pulmonary infiltrate
    • strokes or transient ischemic attacks


Estimated Enrollment: 29
Study Start Date: August 2014
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LentiGlobin BB305 Drug Product (before v6.0 protocol)
Subjects will receive treatment of LentiGlobin BB305 Drug Product manufactured with autologous CD34+ hematopoietic stem cells collected by bone marrow harvest transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene.
Genetic: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Other Name: autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene
Experimental: LentiGlobin BB305 Drug Product (v6.0 protocol)
Subjects will receive treatment of LentiGlobin BB305 Drug Product manufactured with autologous CD34+ hematopoietic stem cells collected by bone marrow harvest transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene.
Genetic: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Other Name: autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene
Experimental: LentiGlobin BB305 Drug Product and plerixafor (v6.0 protocol)
Plerixafor mobilization and apheresis will be used for collection of rescue cells and exploratory manufacturing development. Subjects will receive treatment of LentiGlobin BB305 Drug Product manufactured with autologous CD34+ hematopoietic stem cells collected by bone marrow harvest transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene.
Genetic: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Other Name: autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene
Biological: Plerixafor
Plerixafor is administered by subcutaneous injection prior to apheresis.

Detailed Description:
Subject participation for this study will be 2 years post-treatment. 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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 years of age or older.
  2. Diagnosis of sickle cell disease (SCD), with either βS/βS or βS/β0 or βS/β+ genotype.
  3. Have severe SCD. i.e., in the setting of appropriate supportive care measures for SCD (e.g., pain management plan, hydroxyurea), as judged by the Investigator, have experienced one or more of the following events:

    • Recurrent severe vaso occlusive crises (VOC) (at least 2 episodes per year in the preceding 2 years or in the 2 years prior to initiation of a regular transfusion program).
    • Acute Chest Syndrome (ACS) (at least 2 total episodes in the prior 2 years, with at least one episode in the past year or in the year prior to the initiation of a regular transfusion program), defined as an acute event with pneumonia-like symptoms and the presence of a new pulmonary infiltrate.
    • History of an overt stroke, defined as a sudden neurologic change lasting more than 24 hours that is accompanied by cerebral MRI changes.
    • Echocardiographic evidence of a tricuspid regurgitant jet velocity (TRJV) of > 2.5 m/s.
  4. Medically eligible to undergo hematopoietic stem cell transplant (HSCT).
  5. Karnofsky performance status of ≥ 60.
  6. Subjects should be determined by the investigator to have no physical limitations to undergo general anesthesia and to provide adequate bone marrow harvest from bilateral post-superior iliac sites.

Exclusion Criteria:

  1. Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).
  2. Positive for any active infection.
  3. Any major organ dysfunction (renal, liver, lung and cardiac abnormalities).
  4. Inadequate bone marrow function, as defined by an absolute neutrophil count of < 1000/µL (< 500/µL for subjects on hydroxyurea treatment) or a platelet count < 150,000/µL.
  5. Moyamoya disease on cerebral MRI. Subjects with a history of a revascularization procedure for Moyamoya disease (e.g., encephaloduroarteriosynangiosis (EDAS) procedure) are eligible if the procedure occurred > 1 year prior to study entry.
  6. Contraindication to anesthesia for bone marrow harvesting.
  7. Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
  8. Prior receipt of an allogeneic transplant.
  9. Immediate family member with a known or suspected Familial Cancer Syndrome
  10. Pregnancy, or breastfeeding in a postpartum female, or absence of adequate contraception for fertile subjects.
  11. Participation in another clinical study with an investigational drug within 30 days of Screening.
  12. Prior receipt of gene therapy.
  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 ClinicalTrials.gov identifier: NCT02140554

Contacts
Contact: bluebird bio clinicaltrials@bluebirdbio.com

Locations
United States, California
Recruiting
Oakland, California, United States
United States, Illinois
Recruiting
Chicago, Illinois, United States
United States, Maryland
Recruiting
Bethesda, Maryland, United States
United States, New York
Recruiting
New York, New York, United States
United States, Pennsylvania
Recruiting
Philadelphia, Pennsylvania, United States
United States, South Carolina
Recruiting
Charleston, South Carolina, United States
Sponsors and Collaborators
bluebird bio
Investigators
Study Director: Mohammed Asmal, MD, PhD bluebird bio, Inc.
  More Information

Responsible Party: bluebird bio
ClinicalTrials.gov Identifier: NCT02140554     History of Changes
Other Study ID Numbers: HGB-206
Study First Received: May 14, 2014
Last Updated: March 1, 2017

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 25, 2017