Beta Thalassemia MajorPhase 1/2NCT03276455
Gene Therapy for Beta-Thalassemia Major Using Autologous Hematopoietic Stem Cell Genetically Modified
A Phase 1/2 study testing Autologous CD34+ cells genetically modified in people with Beta Thalassemia Major, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial 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 hematopoietic stem cell transduced with lentiviral vector for the treatment of beta-thalassemia major. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Beta Thalassemia Major
- What is being tested?
- Autologous CD34+ cells genetically modified
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 15 Sep 2017to 15 Sep 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- ≥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.
Who cannot join
- 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.
Show all 18Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Nanfang Hospial
Guangzhou, Guangdong, 510515
ChunFu Li, PhD, 86-020-61641921, chunfugzcn@126.com
ChunFu Li, PhD
About this study
Official title: Evaluation of Safety and Efficacy of Transplantation of Autologous Hematopoietic Stem Cell Genetically Modified in Beta-Thalassemia Major
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 hematopoietic stem cell transduced with lentiviral vector for the treatment of beta-thalassemia major.
Read the 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.
- Conditions
- Beta Thalassemia Major
- Being tested
- Autologous CD34+ cells genetically modified
- Keywords
- Beta thalassemia, Gene therapy, Beta-globin, Hematopoietic stem cells, Lentiviral vector
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous CD34+ cells genetically modifiedGenetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Genetic: Autologous CD34+ cells genetically modified |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of adverse events
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.
Measured: 0-36 months after transplantation
hemoglobin conten
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.
Measured: 3-36 months after transplantation
Secondary outcomes (4)
Hematopoietic stem cell engraftment
Success and kinetics of hematopoietic stem cell engraftment.
Measured: 42 days after transplantation
RCL
The generation of a replication-competent lentivirus (RCL).
Measured: 1-36 months after transplantation
VCN
Quantify gene transfer efficiency and expression by evaluation of average vector copy number(VCN) in blood or bone marrow cells.
Measured: 1-36 months after transplantation
bete-globin content
Evaluate the efficacy of treatment by detection of bete-globin content of HGB of peripheral blood cells.
Measured: 1-36 months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study start15 Sep 2017 (estimated)
- Primary completion15 Sep 2020 (estimated)
- Study completion15 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Beta Thalassemia MajorStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Guangdong Yike Gene Science and Technology CO.,Ltd
- Responsible party
- Principal investigator, Chunfu Li, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03276455
- Sponsor's protocol ID
- NanFangHospital
- Status last verified
- Sep 2017
- First submitted
- 6 Sep 2017
- Last updated
- 8 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Safety and Efficacy of Transplantation of Autologous Hematopoietic Stem Cell Genetically Modified in Beta-Thalassemia Major
- ClinicalTrials.gov ID
- NCT03276455
- Acronym / sponsor ID
- NanFangHospital
- Conditions
- Beta Thalassemia Major
- Keywords
- Beta thalassemia, Gene therapy, Beta-globin, Hematopoietic stem cells, Lentiviral vector
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Collaborators
- Guangdong Yike Gene Science and Technology CO.,Ltd
- Study start
- 15 Sep 2017 (estimated)
- Primary completion
- 15 Sep 2020 (estimated)
- Study completion
- 15 Sep 2021 (estimated)
- First posted
- 8 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 hematopoietic stem cell transduced with lentiviral vector for the treatment of beta-thalassemia major.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Genetic: Autologous CD34+ cells genetically modifiedBeta-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). |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous CD34+ cells genetically modifiedAutologous 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. | Genetic | Experimental |
Primary outcome
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.
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.
4 secondary outcomes
Hematopoietic stem cell engraftment
Time frame: 42 days after transplantation
RCL
Time frame: 1-36 months after transplantation
VCN
Time frame: 1-36 months after transplantation
bete-globin content
Time frame: 1-36 months after transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2017.
- Individual participant dataSharing planned: No
Related trials for Beta Thalassemia Major
Active, not recruiting
Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.
Transfusion-dependent Beta-Thalassemia
RecruitingObservational study
Growth and Development-related Outcomes in Children With Transfusion-dependent Beta-thalassemia After Gene Therapy
Transfusion-dependent Beta-Thalassemia, Gene Therapy
Not yet recruiting
Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
Beta-Thalassemia
RecruitingPhase 1/2
β-Thalassemia Treatment With KL003 Cell Injection
Transfusion-dependent Beta-Thalassemia
Active, not recruitingPhase 3
A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous CD34+ cells genetically modified in people with Beta Thalassemia Major, run by Nanfang Hospital, Southern Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chunfu Li, PhD (86-020-61641921, chunfugzcn@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence of adverse events (time frame: 0-36 months after transplantation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2017.