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

Primary Purpose

Fanconi Anemia

Status

Unknown status

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Gene-modified autologous stem cells

About this trial

This is an interventional treatment trial for Fanconi Anemia focused on measuring Fanconi anemia, Lentiviral vector, FANCA, Gene

Eligibility Criteria

2 Years - 20 Years (Child, Adult)All SexesDoes not accept 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.

Sites / Locations

Capital Institute of Pediatrics affiliated Children's hospitalRecruiting
Beijing Children's HospitalRecruiting
Shenzhen Geno-immune Medical InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gene-modified autologous stem cells

Arm Description

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

Outcomes

Primary Outcome Measures

Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events

Physiological parameter (measuring cytokine response, fever, symptoms)

Secondary Outcome Measures

Treatment responses

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

Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.

Full Information

NCT ID

NCT03351868

First Posted

November 20, 2017

Last Updated

September 18, 2019

Sponsor

Shenzhen Geno-Immune Medical Institute

1. Study Identification

Unique Protocol Identification Number

NCT03351868

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Unknown status

Study Start Date

December 1, 2017 (Actual)

Primary Completion Date

December 31, 2020 (Anticipated)

Study Completion Date

December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shenzhen Geno-Immune Medical Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fanconi Anemia

Keywords

Fanconi anemia, Lentiviral vector, FANCA, Gene

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Gene-modified autologous stem cells

Arm Type

Experimental

Arm Description

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

Intervention Type

Genetic

Intervention Name(s)

Gene-modified autologous stem cells

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events

Description

Physiological parameter (measuring cytokine response, fever, symptoms)

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Treatment responses

Description

Time Frame

1 year

Title

Quality of life

Description

Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lung-Ji Chang, Ph.D

Phone

86-13671121909

c@szgimi.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lung-Ji Chang, Ph.D

Organizational Affiliation

Shenzhen Geno-Immune Medical Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

Capital Institute of Pediatrics affiliated Children's hospital

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Jie Zheng, M.D./Ph. D

Organizational Affiliation

Beijing Children's Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Capital Institute of Pediatrics affiliated Children's hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100020

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

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

Phone

+86-13911601076

xsusan28@sina.com

First Name & Middle Initial & Last Name & Degree

Lixiao Shi, M.M.

Phone

+86-18810963129

13780524314@163.com

Facility Name

Beijing Children's Hospital

City

Beijing

State/Province

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jie Zheng, MD/PhD

Phone

+86-13683284467

cutezjie@163.com

Facility Name

Shenzhen Geno-immune Medical Institute

City

Shenzhen

State/Province

Guangdong

ZIP/Postal Code

518000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lung-Ji Chang, PhD

Phone

86-075586725195

c@szgimi.org

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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