- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03276455
Gene Therapy for Beta-Thalassemia Major Using Autologous Hematopoietic Stem Cell Genetically Modified
Evaluation of Safety and Efficacy of Transplantation of Autologous Hematopoietic Stem Cell Genetically Modified in Beta-Thalassemia Major
Study Overview
Status
Conditions
Intervention / Treatment
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 ineffective erythropoiesis, hemolysis and anemia. Transplantation of allogeneic hematopoietic stem cells (HSCT) is the only available cure which is, however, has the significant risk of transplant related mortality, graft versus host disease and limited source. Therefore, transplantation of autologous hematopoietic stem cells will be an attractive therapeutic treatment for beta-thalassemia major patients. 10 patients will be treated with genetically modified autologous hematopoietic stem cells which transduced with lentiviral vector encoding for beta-globin gene.
Patients will participate for this study for 3 years.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: ChunFu Li, PhD
- Phone Number: 86-020-61641921
- Email: chunfugzcn@126.com
Study Contact Backup
- Name: Zhiyong Peng
- Phone Number: 86-020-61641925
- Email: pengzhiyong8@163.com
Study Locations
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510515
- Nanfang Hospial
-
Contact:
- ChunFu Li, PhD
- Phone Number: 86-020-61641921
- Email: chunfugzcn@126.com
-
Principal Investigator:
- ChunFu Li, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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 Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Experimental
Beta-thalassemia major subjects who are 8 years age or older are transplated by autologous CD34+ cells genetically modified(autologous hematopoietic stem cell transduced with lentiviral vector encoding the therapeutic beta-globin gene).
|
Autologous hematopoietic stem cell transduced with lentiviral vector encoding the therapeutic beta-globin gene.
The target dose in the transduced product is 3x10^6 cells/Kg CD34+ cells, with a minimum dose of 2 x 10^6/Kg and a maximum dose of 20 x 10^6/Kg, depending on the yield of cells.
The product will be injected intraosseously following intravenous BU ±Flu ±Cy.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
incidence of adverse events
Time Frame: 0-36 months after transplantation
|
Evaluate the safety of treatment with transplantation of autologous hematopoietic stem cell transduced with lentiviral vector encoding the therapeutic beta-globin gene as measured by the incidence of adverse events.
|
0-36 months after transplantation
|
hemoglobin conten
Time Frame: 3-36 months after transplantation
|
Evaluate the efficacy of treatment with transplantation of autologous hematopoietic stem cell transduced with lentiviral vector encoding the therapeutic beta-globin gene by the detection hemoglobin content of peripheral blood cells.
|
3-36 months after transplantation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hematopoietic stem cell engraftment
Time Frame: 42 days after transplantation
|
Success and kinetics of hematopoietic stem cell engraftment.
|
42 days after transplantation
|
RCL
Time Frame: 1-36 months after transplantation
|
The generation of a replication-competent lentivirus (RCL).
|
1-36 months after transplantation
|
VCN
Time Frame: 1-36 months after transplantation
|
Quantify gene transfer efficiency and expression by evaluation of average vector copy number(VCN) in blood or bone marrow cells.
|
1-36 months after transplantation
|
bete-globin content
Time Frame: 1-36 months after transplantation
|
Evaluate the efficacy of treatment by detection of bete-globin content of HGB of peripheral blood cells.
|
1-36 months after transplantation
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NanFangHospital
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Beta Thalassemia Major
-
CelgeneTerminatedBeta Thalassemia Intermedia | Beta Thalassemia MajorFrance, United Kingdom, Italy, Greece
-
M.D. Anderson Cancer CenterWithdrawnSickle Cell Disease | Sickle Beta Thalassemia | Beta Thalassemia Major | Sickle Cell-SS Disease | Sickle Beta 0 Thalassemia | Sickle Beta Plus ThalassemiaUnited States
-
CorrectSequence Therapeutics Co., LtdNot yet recruitingBeta-Thalassemia MajorChina
-
First Affiliated Hospital of Guangxi Medical UniversityUnknown
-
Editas Medicine, Inc.RecruitingHemoglobinopathies | Thalassemia Major | Thalassemia Intermedia | Transfusion Dependent Beta ThalassemiaUnited States, Canada
-
Aga Khan UniversityCompletedBeta Thalassemia Major
-
China Medical University HospitalCompleted
-
EmeraMedCompletedBeta Thalassemia MajorAlbania
-
Tanta UniversityCompletedBeta Thalassemia MajorEgypt
-
Ain Shams UniversityUnknownBeta Thalassemia MajorEgypt
Clinical Trials on Autologous CD34+ cells genetically modified
-
AdaptimmuneActive, not recruitingHepatocellular Cancer | AFP Expressing TumorsUnited States, United Kingdom, France, Spain
-
AdaptimmuneActive, not recruitingMelanoma | Head and Neck Cancer | Gastric Cancer | Esophageal Cancer | Ovarian Cancer | Non-Small Cell Lung Cancer | Urinary Bladder Cancer | Synovial Sarcoma | Gastroesophageal Junction | Myxoid Round Cell LiposarcomaUnited States, Canada
-
AdaptimmuneCompletedCarcinoma | Non-Small Cell Lung CancerUnited States, Spain, United Kingdom, Canada
-
AdaptimmuneCompletedMelanoma | Head and Neck Cancer | Urothelial Carcinoma | Bladder Urothelial CarcinomaUnited States, Canada, Spain
-
AdaptimmuneTerminated
-
GlaxoSmithKlineCompleted
-
AdaptimmuneICON plcTerminatedEsophageal Cancer | Esophagogastric Junction CancerUnited States, Canada, United Kingdom, Spain, France
-
IRCCS San RaffaeleFondazione TelethonActive, not recruiting
-
University of CologneUnknownCD30 Positive Cutaneous T Cell Lymphoma | CD30 Positive Transformed Mycosis FungoidesGermany