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

NCT ID: NCT03351868

Last Updated: 2019-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-01

Study Completion Date

2021-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Fanconi Anemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gene-modified autologous stem cells

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

Group Type EXPERIMENTAL

Gene-modified autologous stem cells

Intervention Type GENETIC

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

Interventions

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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

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of Fanconi anemia FANCA type based on DNA sequencing and sensitivity test for chromosomal cleavage by mitomycin C or butylene oxide.
2. No cytogenetic abnormalities and the proportion of myelodysplastic abnormalities does not exceed 5% within 3 months prior to stem cell collection.
3. Age: ≥ 4 years.
4. Karnofsky: ≥ 70%.
5. ANC ≥ 5×10\^8/L; PLT ≥ 2×10\^10/L.
6. Hemoglobin ≥ 8g/dL.
7. 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.
8. Pulmonary function is normal; DLCO \> 50%.
9. Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria

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

2 Years

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role lead

Responsible Party

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Lung-Ji Chang

President

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lung-Ji Chang, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Geno-Immune Medical Institute

Xiao-Dong Shi, M.D./Ph. D

Role: STUDY_DIRECTOR

Capital Institute of Pediatrics affiliated Children's hospital

Jie Zheng, M.D./Ph. D

Role: STUDY_DIRECTOR

Beijing Children's Hospital

Locations

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Capital Institute of Pediatrics affiliated Children's hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Beijing Children's Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lung-Ji Chang, Ph.D

Role: CONTACT

86-13671121909

Facility Contacts

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XiaoDong Shi, M.D./P.H.D

Role: primary

+86-13911601076

Lixiao Shi, M.M.

Role: backup

+86-18810963129

Jie Zheng, MD/PhD

Role: primary

+86-13683284467

Lung-Ji Chang, PhD

Role: primary

86-075586725195

Other Identifiers

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GIMI-IRB-17021

Identifier Type: -

Identifier Source: org_study_id

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