A Phase I/II Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the ß-Hemoglobinopathies (Sickle Cell Anemia and ß-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with a Lentiviral beta-A-T87Q-Globin Vector (LentiGlobin® BB305 Drug Product) - N/A
- Conditions
- Severe sickle cell anemia and transfusion-dependent beta-thalassemia major. This study will enroll patients who are eligible for an allogeneic hematopoietic stem cell transplant (HSCT) but do not have a suitable, willing human leukocyte antigen (HLA)-identical sibling donor.MedDRA version: 14.1 Level: LLT Classification code 10055579 Term: Sickle-cell beta thalassemia System Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2012-000695-42-FR
- Lead Sponsor
- bluebird bio, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 7
All subjects must:
1.Be between 5 and 35 years of age, inclusive.
•Adult subjects (between 18 and 35 years of age, inclusive, at the time of consent) must be able to provide written consent.
•For pediatric subjects (between 5 and 17 years of age, inclusive, at the time of consent), a competent parent or legal guardian must be able to provide written informed consent. When possible, involvement of the child >7 years of age in the decision is highly recommended, and written assent will be obtained and should be clearly documented.
•Subjects aged 5 to 14 years require the approval from the Comité de Surveillance prior to enrollment.
2.Have severe SCA or transfusion dependent beta-ThalM, regardless of the genotype (e.g., ß0, ß+, ßE/ß0, ßS/ßS, ßS/ß0), with the diagnosis confirmed by Hb studies. Subjects with transfusion dependent beta-ThalM must be stable and maintained on an appropriate iron chelation regimen. Transfusion dependence is defined as requiring at least 100 mL/kg/year of packed RBCs.
3.Be candidates for HSCT.
4.Be willing and able, in the Investigator’s opinion, to comply with the study procedures outlined in the study protocol. If a pediatric subject, the subject’s parent/legal guardian also must be willing and able to comply with the study procedures outlined in the study protocol.
5.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 SCA also must:
6.Have 1 or more of the following poor prognostic risk factors despite having had adequate therapy (at least 4 months duration) with hydroxyurea (unless they were unable to tolerate hydroxyurea therapy):
•Recurrent VOC and/or priapism (at least 2 episodes in the preceding year or in the year prior to start of a regular transfusion program).
•Presence of cerebral vasculopathy requiring a long term transfusion program (at least 6 months).
•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.
•Red cell alloimmunization (>2 antibodies).
•Presence of sickle cell cardiomyopathy documented by Doppler echocardiography.
•Recurrent acute chest syndrome (at least 2 episodes in the preceding year) defined by the presence of a new pulmonary infiltrate involving at least 1 complete lung segment (but excluding atelectasis) associated with at least 1 new symptom: chest pain, fever (>38.5°C), tachypnea, wheezing or cough not explained by infection. Subjects with a chronic oxygen saturation <90% (excluding periods of SCA crisis) or carbon dioxide diffusing capacity (DLco) less than 60% in the absence of an infection should not be included in the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this
All subjects must not meet any of the following:
1.Availability of a suitable, willing HLA identical sibling.
2.Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2), human T lymphotrophic virus 1 (HTLV 1), vesicular stomatitis virus G (VSV G) antibody or VSV G ribonucleic acid (RNA).
3.Clinically significant, active bacterial, viral, or fungal infection.
4.Contraindication to anesthesia for bone marrow harvesting.
5.Any prior or current malignancy, myeloproliferative or immunodeficiency disorder.
6.A white blood cell (WBC) count <3×10^9/L and/or platelet count <120×10^9/L.
7.Receipt of an allogeneic transplant.
8.Receipt of erythropoietin within 3 months before HSCT harvest.
9.Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers).
10.Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study.
11.History of malaria relapses in the absence of recent infection.
12.History of complex allo immunization, which could cause difficulty administering transfusions.
13.Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects. Females of child bearing potential must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or contraceptive implant/injection throughout the 27 month study period.
14.History of major organ damage including:
•Liver disease, as evidenced by transaminase levels >3× upper limit of normal or the presence of histopathological evidence of liver cirrhosis 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 MRI.
•Evidence of significant pulmonary hypertension.
15.Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician.
16.Participation in another clinical study with an investigational drug within 30 days of screening.
17.Subjects who have the desire to become a parent within the 27 month study period.
18.Prior receipt of gene therapy.
19.An assessment by the Investigator that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
Subjects with beta-ThalM also must not:
Be Pesaro Class III (poor compliance of iron chelation therapy, presence of hepatomegaly, and severe fibrosis) (Lucarelli et al., 2001).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method