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

• ClinicalTrials.gov Identifier: NCT03351868
• Recruitment Status: Unknown
• First Posted: November 24, 2017
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: November 20, 2017
• First Posted Date: November 24, 2017
• Last Update Posted Date: September 19, 2019
• Actual Study Start Date: December 1, 2017
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2017)

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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 17, 2018)

• 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
• 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.

Original Secondary Outcome Measures (submitted: November 20, 2017)

• Treatment responses [ Time Frame: 1 year ]
  Blood routine indexes will be got 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 [ Time Frame: 1 year ]
  Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Fanconi Anemia

Intervention

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

Study Arms

Experimental: Gene-modified autologous stem cells

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

Intervention: Genetic: Gene-modified autologous stem cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 17, 2018): 10
• Original Estimated Enrollment (submitted: November 20, 2017): 30
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 20 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03351868
• Other Study ID Numbers: GIMI-IRB-17021
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019