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
A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in Severe Sickle Cell Disease
Sponsors
Source
bluebird bio
Oversight Info
Has Dmc
Yes
Brief Summary
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 hematopoietic stem cell
(HSC) transplantation (HSCT) using LentiGlobin BB305 Drug Product.
Detailed Description
Subject participation for this study will be 2 years post-transplant. 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.
Overall Status
Recruiting
Start Date
2014-08-01
Completion Date
2020-08-01
Primary Completion Date
2020-08-01
Phase
Phase 1
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Safety |
1-24 months post-transplant |
Secondary Outcome
Measure |
Time Frame |
|
Clinical efficacy will be evaluated by comparing the frequency of clinical events secondary to sickle cell disease |
1-24 months post-transplant |
Enrollment
29
Condition
Intervention
Intervention Type
Genetic
Intervention Name
Description
LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Arm Group Label
Group A
Group B
Group C
Other Name
autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene
Intervention Type
Biological
Intervention Name
Description
Plerixafor is administered by subcutaneous injection prior to apheresis.
Arm Group Label
Group B
Group C
Eligibility
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:
- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2),
hepatitis B virus (HBV), or hepatitis C (HCV).
- Clinically significant and active bacterial, viral, fungal, or parasitic infection.
- 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.
- 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.
- Contraindication to anesthesia for bone marrow harvesting.
- Contraindication to plerixafor or busulfan.
- Any prior or current malignancy or immunodeficiency disorder, except previously
treated, non-life threatening, cured tumors such as squamous cell carcinoma of the
skin.
- Prior receipt of an allogeneic transplant.
- Immediate family member with a known or suspected Familial Cancer Syndrome.
- Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception
for fertile subjects.
- Participation in another clinical study with an investigational drug within 30 days of
Screening.
- Subjects who have the desire to become a parent within the study period.
- Prior receipt of gene therapy.
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Mohammed Asmal, MD, PhD |
Study Director |
bluebird bio, Inc. |
Overall Contact
Location
Facility |
Status |
|
Oakland California United States |
Recruiting |
|
Chicago Illinois United States |
Recruiting |
|
Bethesda Maryland United States |
Recruiting |
|
New York New York United States |
Recruiting |
|
Philadelphia Pennsylvania United States |
Recruiting |
|
Charleston South Carolina United States |
Recruiting |
Location Countries
Country
United States
Verification Date
2017-09-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Has Expanded Access
No
Condition Browse
Number Of Arms
3
Intervention Browse
Mesh Term
JM 3100
Arm Group
Arm Group Label
Group A
Arm Group Type
Experimental
Description
Subjects will have rescue cells collected by bone marrow harvest, and 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.
Arm Group Label
Group B
Arm Group Type
Experimental
Description
Group B1:
Subjects will have rescue cells collected by bone marrow harvest, and 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.
Group B2:
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.
Arm Group Label
Group C
Arm Group Type
Experimental
Description
Plerixafor mobilization and apheresis will be used for collection of rescue cells, and subjects will receive treatment of LentiGlobin BB305 Drug Product manufactured with autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and apheresis transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene.
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
May 14, 2014
Study First Submitted Qc
May 14, 2014
Study First Posted
May 16, 2014
Last Update Submitted
September 6, 2017
Last Update Submitted Qc
September 6, 2017
Last Update Posted
September 11, 2017
ClinicalTrials.gov processed this data on August 23, 2018
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.