This trial is active, not recruiting.

Conditions beta-thalassemia major, sickle cell disease
Treatment lentiglobin bb305 drug product
Phase phase 1/phase 2
Sponsor bluebird bio
Start date July 2013
End date December 2017
Trial size 7 participants
Trial identifier NCT02151526, 2012-000695-42, HGB-205


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).

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 (autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q-globin gene)
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.

Primary Outcomes

Success and kinetics of hematopoietic stem cell (HSC) engraftment
time frame: 1-24 months post-transplant
Incidence of transplant related mortality through 100 days post treatment
time frame: 1-24 months post-transplant
Overall survival
time frame: 1-24 months post-transplant
Detection of vector derived replication-competent lentivirus (RCL) in any subject
time frame: 1-24 months post-transplant
Characterization of events of insertional mutagenesis leading to clonal dominance or leukemia
time frame: 1-24 months post-transplant
Monitoring of laboratory parameters and frequency and severity of clinical AEs
time frame: 1-24 months post-transplant

Secondary Outcomes

Quantify gene transfer efficiency and expression by evaluation
time frame: 1-24 months post-transplant
Quantify gene transfer efficiency and expression by evaluation
time frame: 1-24 months post-transplant
time frame: 1-24 months post-transplant
time frame: 1-24 months post-transplant

Eligibility Criteria

Male or female participants from 5 years up to 35 years old.

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.

Additional Information

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)
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by bluebird bio.