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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03351868
Recruitment Status : Unknown
Verified September 2019 by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute.
Recruitment status was:  Recruiting
First Posted : November 24, 2017
Last Update Posted : September 19, 2019
Information provided by (Responsible Party):
Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : December 1, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021

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

Primary Outcome Measures :
  1. Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [ Time Frame: 6 months ]
    Physiological parameter (measuring cytokine response, fever, symptoms)

Secondary Outcome Measures :
  1. Treatment responses [ Time Frame: 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

  2. Quality of life [ Time Frame: 1 year ]
    Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03351868

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Contact: Lung-Ji Chang, Ph.D 86-13671121909

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China, Beijing
Capital Institute of Pediatrics affiliated Children's hospital Recruiting
Beijing, Beijing, China, 100020
Contact: XiaoDong Shi, M.D./P.H.D    +86-13911601076   
Contact: Lixiao Shi, M.M.    +86-18810963129   
Beijing Children's Hospital Recruiting
Beijing, Beijing, China
Contact: Jie Zheng, MD/PhD    +86-13683284467   
China, Guangdong
Shenzhen Geno-immune Medical Institute Recruiting
Shenzhen, Guangdong, China, 518000
Contact: Lung-Ji Chang, PhD    86-075586725195   
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
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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
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Responsible Party: Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute Identifier: NCT03351868    
Other Study ID Numbers: GIMI-IRB-17021
First Posted: November 24, 2017    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute:
Fanconi anemia
Lentiviral vector
Additional relevant MeSH terms:
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Fanconi Syndrome
Fanconi Anemia
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Congenital Bone Marrow Failure Syndromes
Bone Marrow Failure Disorders
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases