FANCA Gene Transfer for Fanconi Anemia Using a High-safety, High-efficiency, Self-inactivating Lentiviral Vector

Sponsor

Shenzhen Geno-Immune Medical Institute (Other)

Overall Status

Unknown status

CT.gov ID

NCT03351868

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase I/II clinical trial of gene therapy for treating Fanconi anemia using a self-inactivating lentiviral vector to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.

Condition or Disease	Intervention/Treatment	Phase
Fanconi Anemia	Genetic: Gene-modified autologous stem cells	N/A

Detailed Description

Fanconi anemia is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The major problem for most patients is aplastic anemia, the blood counts for red blood cells, white blood cells, and platelets are low. In addition, some patients have physical defects usually involving the skeleton and kidneys. Fanconi anemia is typically diagnosed in childhood, and there is a high fatality rate. Hematopoietic stem cell transplantation (HSCT) is a common treatment for Fanconi anemia. However, there are many risks associated with HSCT including rejection of the transplanted cells and graft-versus-host disease.

The primary objectives are to evaluate the safety of the self-inactivating lentiviral vector, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming immune abnormalities present at the time of treatment, assessment of gene correction efficiency, and finally the long-term correction of Fanconi anemia associated disease symptoms.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Gene Transfer for Fanconi Anemia Using a Self-inactivating Lentiviral Vector

Actual Study Start Date :

Dec 1, 2017

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gene-modified autologous stem cells Autologous hematopoeitic stem cells and mesenchymal stem cells transduced with lentiviral vector carrying the FANCA gene ex vivo	Genetic: Gene-modified autologous stem cells Infusion for 5x10^6~1x10^7 per kilogram of body weight of gene-modified cells; or more infusions depending on the circumstances

Arm

Intervention/Treatment

Experimental: Gene-modified autologous stem cells

Autologous hematopoeitic stem cells and mesenchymal stem cells transduced with lentiviral vector carrying the FANCA gene ex vivo

Genetic: Gene-modified autologous stem cells

Infusion for 5x10^6~1x10^7 per kilogram of body weight of gene-modified cells; or more infusions depending on the circumstances

Outcome Measures

Primary Outcome Measures

Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [6 months]
Physiological parameter (measuring cytokine response, fever, symptoms)

Secondary Outcome Measures

Treatment responses [1 year]
Blood routine indexes will be obtained before and after treatment. Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
Quality of life [1 year]
Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of Fanconi anemia FANCA type based on DNA sequencing and sensitivity test for chromosomal cleavage by mitomycin C or butylene oxide.
No cytogenetic abnormalities and the proportion of myelodysplastic abnormalities does not exceed 5% within 3 months prior to stem cell collection.
Age: ≥ 4 years.
Karnofsky: ≥ 70%.
ANC ≥ 5×10^{8/L; PLT ≥ 2×10}10/L.
Hemoglobin ≥ 8g/dL.
Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with

serum creatinine ≤ 1.5×ULN;
serum bilirubin ≤ 3×ULN;
AST/ALT ≤ 5×ULN.

Pulmonary function is normal; DLCO > 50%.
Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

Diagnosis of active malignant disease or myelodysplastic syndrome.
Diagnosis of myeloid leukemia.
Pregnant or lactating females.
Existence of an available HLA-identical related donor.
Subject infected with HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.
Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Capital Institute of Pediatrics affiliated Children's hospital	Beijing	Beijing	China	100020
2	Beijing Children's Hospital	Beijing	Beijing	China
3	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong	China	518000

Sponsors and Collaborators

Shenzhen Geno-Immune Medical Institute

Investigators

Principal Investigator: Lung-Ji Chang, Ph.D, Shenzhen Geno-Immune Medical Institute
Study Director: Xiao-Dong Shi, M.D./Ph. D, Capital Institute of Pediatrics affiliated Children's hospital
Study Director: Jie Zheng, M.D./Ph. D, Beijing Children's Hospital