Status:
UNKNOWN
Gene Therapy for Beta-Thalassemia Major Using Autologous Hematopoietic Stem Cell Genetically Modified
Lead Sponsor:
Nanfang Hospital, Southern Medical University
Collaborating Sponsors:
Guangdong Yike Gene Science and Technology CO.,Ltd
Conditions:
Beta Thalassemia Major
Eligibility:
All Genders
8+ years
Phase:
PHASE1
PHASE2
Brief Summary
This is a single group, open label study in 10 subjects who are 8 years of age or older with beta-thalassemia major. The objective of this study is to evaluate the safety and efficacy of autologous he...
Detailed Description
Beta-thalassemia major is a life-threatening genetic disease of red cell malfunction. It is caused by mutations in the beta-globin gene which encodes the beta-globin protein, leading to the ineffectiv...
Eligibility Criteria
Inclusion
- Subjects must be 8 years of age or older.
- Subjects or their parents/legal guardians must be able to understand and voluntarily sign an informed consent form.
- Subjects must have a confirmed diagnosis of ß-thalassemia major and
- ≥100 mL/kg/year of pRBCs or ≥ 8 transfusions of pRBCs per year over a minimum of two years prior to entry onto the study.
- Subjects must be in clinically stable condition and eligible for hematopoietic stem cell transplantation.
- Subjects must satisfy Karnofsky index ≥80% for adults or Lansky index
- ≥70% for children.
- Subjects must have survival expectancy of greater than 6 months.
- Subjects must have been treated and followed up for at least the past 2 years in specialized institutions where they have comprehensive assessment of the disease（including psychiatric assessment），and detailed medical materials at least the past 2years so as to self-contrast before and after treatment.
- Subjects must discontinue treatment of hydroxyurea, 5-azoside or cytarabine at least three months prior to entry onto the study.
Exclusion
- Having an HLA-matched donor(sibling or of a suitable 10/10 matched unrelated donor).
- Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA (or negative HCV RNA but on antiviral treatment).
- Contraindication to anesthesia for bone marrow collection.
- Severe, bacterial, active viral, or fungal infection, etc.
- The history of malignant tumor.
- The white blood cell (WBC) count \<3000/uL and/or platelet count \<100,000/uL exclude hypersplenism factor.
- Family history of familial cancer syndromes (including but not limited to Hereditary breast and ovarian syndrome, hereditary non-polyp colorectal cancer syndrome, familial adenomatous polyposis).
- Previous allogeneic bone marrow transplantation.
- The history of psychosis and any psychiatric disorder.
- Active substance abuse, drug or alcohol abuse recently.
- The history of complex allo-immunization which could cause difficulty administering transfusions.
- Female adults who are pregnant , breast feeding or lack of effective contraception.
- History of major organ damage including:
- Severe cerebrovascular disease or cognitive sequelae, including hemiplegia. Severe liver disease with alanine transaminase (ALT) \>3 upper limit of normal. Severe liver cirrhosis or fibrosis on liver biopsy. Heart disease with ejection fraction\<25% or T2\* \<10 ms by magnetic resonance imaging (MRI). Kidney disease with creatinine clearance \<30% normal value. Lung disease, including pulmonary fibrosis, pulmonary arterial hypertension or pulmonary function tests below standard (i.e., pO2\<90 mmHg and/or carbon dioxide diffusion coefficient\<50%). Endocrine disorder including insulin dependent diabetes mellitus, Hyperthyroidism or deficiency, Hyperparathyroidism or deficiency.
- Participation in another clinical study within 30 days of screening.
- Subjects with severe iron overload determined by the researchers.
- Any other situation that unsuitably undergoing hematopoietic stem cell transplantation determined by the physicians or researchers.
- Presence of chromosomal abnormalities by bone marrow detected.
Key Trial Info
Start Date :
September 15 2017
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 15 2021
Estimated Enrollment :
10 Patients enrolled
Trial Details
Trial ID
NCT03276455
Start Date
September 15 2017
End Date
September 15 2021
Last Update
September 8 2017
Active Locations (1)
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1
Nanfang Hospial
Guangzhou, Guangdong, China, 510515