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

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

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.

Study Overview

• Status: Unknown
• Conditions: Fanconi Anemia
• Intervention / Treatment: Genetic: Gene-modified autologous stem cells

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
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Capital Institute of Pediatrics affiliated Children's hospital
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Children's Hospital
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 20 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events	Physiological parameter (measuring cytokine response, fever, symptoms)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1 year
Quality of life	Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2017
• Primary Completion (ANTICIPATED): December 31, 2020
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (ACTUAL): November 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Fanconi anemia; Gene; Lentiviral vector; FANCA
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Anemia; Fanconi Syndrome; Fanconi Anemia
• Other Study ID Numbers: GIMI-IRB-17021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No