Thalassemia Treatment Based on the Stem Cell Technology

The Third Affiliated Hospital of Guangzhou Medical University

In order to study the transplantation effect of hematopoetic stem cells from beta-thalassemia induced pluripotent stem cells. We applied clinical grade source of autologous hematopoietic stem cell for the treatment of beta-thalassemia patients, detecting the homing of hematopoietic stem cell transplantation, the differentiation of hematopoietic stem cells in vivo and the hemoglobin beta-chain (HBB) protein expression in the body of recovery, etc., as well as to make a research on the efficacy and safety of hematopoietic stem cells from beta-thalassemia induced pluripotent stem cells.

Study Overview

• Status: Unknown
• Conditions: Beta-Thalassemia
• Intervention / Treatment: Biological: Hematopoetic stem cells

Detailed Description

1. On a Good Manufacturing Practice(GMP) condition, we establish non-exotic of different mutation types of beta-thalassemia -induced pluripotent stem cells（iPS） and make a comparisons of the stability and the differentiation of efficiency of these iPS cells inducing from different sources with foreign gene integration.
2. Using the technique of artificial nuclease and in situ repairmen, we establish efficient system for different beta-thalassemia mutation site and in view of the security of these system.
3. Establish a repaired beta-thalasemia gene mutated differentiation of iPS technology system.
4. Build a functional gene therapy self-limiting slow viruses, optimizing the preparation system and to establish a virus preparation of infection of hematopoietic stem cell technology system under the GMP condition.
5. Establish humanized beta-mice model, evaluate the safety of the iPS cell of gene therapy and efficiency before the clinical experiment.
6. Improve the existing hematopoietic stem cell transplant(HSCT) clinical application solutions, detect rate of graft rejection, rate of transplantation and other indicators, finish the evaluation of application by clinical cases.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. The genetic diagnosis confirmed homozygous for beta to poverty or double heterozygote, clinical severe anemia;
2. Aged 1 ~ 18 years old, no obvious iron overload cause organ damage;
3. Has a suitable donor HLA high resolution;
4. The informed consent

Exclusion Criteria:

1. There has been a significant increase in the level of tumor markers (AFP/CEA/CA199 / CA125) in the past five years.
2. Serious primary diseases such as cardiovascular, liver and hematopoietic systems; Those who have major organs with serious function; An adrenal disease or other disease that causes the organ failure of the organ;
3. An autoimmune disease, a family history of genetic disease, and an abnormal thyroid function;
4. Peripheral blood chromosome checking for nuclear aliens;
5. HIV, hepatitis b or hepatitis c;
6. A person with a history of severe drug allergies or an allergic person;
7. Those who do not expect to live for more than one year;
8. The researchers suggest that the patient may have a potential or have a disorder (such as an uncontrolled infection, right heart failure, pulmonary hypertension) that is interfering with this study.
9. In the first six months, alcohol and other substance abuse were not allowed;
10. Subjects who participated in other clinical trials or participated in other clinical trials within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Patient; Hematopoetic stem cells differentiated from beta-thalassemia induced pluripotent stem cells.	Biological: Hematopoetic stem cells; Patient will inject with hematopoetic stem cells differentiated from beta-thalassemia induced pluripotent stem cells
No Intervention: non-intervention Patient; No treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The check of granulocyte transplantation-granulocyte plant living standards	Granulocyte plant living standards for three days in a row after transplantation granulocyte should be greater than 0.5 x 109 / L,	3 days
The check of granulocyte transplantation-platelet plant living standards	Platelet plant living standard for seven consecutive days after transplantation the platelet should be greater than 20 x 109 / L and infusion.	seven consecutive days
Effect of cell transplantation	The granulocyte plant living standards and platelet plant living standards will be combined to measure the effect of cell transplantation.	seven days

Collaborators and Investigators

• Sponsor: Xiaofang Sun
• Collaborators: Nanfang Hospital of Southern Medical University; Third Affiliated Hospital, Sun Yat-Sen University; Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): June 14, 2016
• Study Completion (Anticipated): December 31, 2017

Study Registration Dates

• First Submitted: June 23, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 17, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: stem cell; thalassemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: 201508020258

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No