Gene Therapy for Beta-Thalassemia Major Using Autologous Hematopoietic Stem Cell Genetically Modified

NCT03276455 | Unknown Phase 1

• 1 other identifier: NanFangHospital
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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 hematopoietic stem cell transduced with lentiviral vector for the treatment of beta-thalassemia major.

Conditions

Beta Thalassemia Major

Keywords

Beta thalassemia; Gene therapy; Beta-globin; Hematopoietic stem cells; Lentiviral vector

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  3-36 months after transplantation

Secondary Outcomes (4)

• Hematopoietic stem cell engraftment

  42 days after transplantation

• RCL

  1-36 months after transplantation

• VCN

  1-36 months after transplantation

• bete-globin content

  1-36 months after transplantation

Study Arms (1)

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).

Genetic: Autologous CD34+ cells genetically modified

Interventions

Autologous CD34+ cells genetically modified GENETIC

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.

Experimental

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• Guangdong Yike Gene Science and Technology CO.,Ltd: collaborator

Study Sites (1)

Nanfang Hospial

Guangzhou, Guangdong, 510515, China

Location

MeSH Terms

Conditions

beta-Thalassemia

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Chunfu Li, PhD

CONTACT

86-020-61641921; chunfugzcn@126.com

Zhiyong Peng

CONTACT

86-020-61641925; pengzhiyong8@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director and professor

Study Record Dates

• First Submitted: September 6, 2017
• First Posted: September 8, 2017
• Study Start: September 15, 2017
• Primary Completion: September 15, 2020
• Study Completion: September 15, 2021
• Last Updated: September 8, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)