Gene Therapy for the Treatment of Fanconi's Anemia Type C

NCT00001399 | Completed Phase 1

• 2 other identifiers: 94003394-H-0033
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Fanconi's Anemia is an inherited disorder that can produce bone marrow failure. In addition, some patients with Fanconi's anemia have physical defects usually involving the skeleton and kidneys. The major problem for most patients is aplastic anemia, the blood counts for red blood cells, white blood cells, and platelets are low because the bone marrow fails to produce these cells. Some patients with Fanconi's anemia can develop leukemia or cancers of other organs. Many laboratory studies have suggested that Fanconi's anemia is caused by an inherited defect in the ability of cells to repair DNA. Recently, the gene for one of the four types of Fanconi's anemia, type C, has been identified. It is known that this gene is defective in patients with Fanconi's anemia type C. Researchers have conducted laboratory studies that suggest Fanconi's anemia type C may be treatable with gene therapy. Gene therapy works by placing a normal gene into the cells of patients with abnormal genes responsible for Fanconi's anemia type C. After the normal gene is in place, new normal cells can develop and grow. Drugs can be given to these patients kill the remaining abnormal cells. The new cells containing normal genes and will not be harmed by these drugs. The purpose of this study is to test whether researchers can safely place the normal Fanconi's anemia type C gene into cells of patients with the disease. The gene will be placed into special cells in the bone marrow called stem cells. These stem cells are responsible for producing new red blood cells, white blood cells, and platelets.

Conditions

Fanconi's Anemia; Pancytopenia

Keywords

Gene Therapy; Stem Cell Rescue; Bone Marrow Failure; Fanconi Anemia

Interventions

Transduced CD34+ Cells DRUG

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria within 30 days prior to study entry (Day 0) unless otherwise noted.
• Males or females, age greater than or equal to 5 years of age.
• Diagnosis of Fanconi anemia, complementation group C, as confirmed by 1) Diepoxybutane or mitomycin C testing and 2) DNA analysis indicating FACC mutations.
• Adequate baseline organ function as assessed by the following laboratory values within 30 days prior to study entry (day -30 to 0).
• Adequate renal function with estimated creatinine clearance greater than 50 ml/min. (This will be determined by serum creatinine and 24-hour urine creatinine ordered concurrently).
• Adequate liver function with SGOT, SGPT and alkaline phosphatase less than or equal to 5 times the ULN (if transaminases greater than the upper limit of normal (ULN), patients should have a hepatitis B surface antigen (HBsAG) test prior to study entry. Patients may not enter the study if HBsAG is positive).
• PT and PTT not more than 1.5 times the ULN.
• Serum Amylase less than or equal to 1.5 times the ULN.
• Bilirubin less than or equal to 3.0 mg/dL.
• Triglyceride less than 400 mg/dl.
• Ability to give informed consent.
• Normal cardiac function by history and exam.
• Resting transcutaneous oxygen saturation greater than 90 percent on room air.
• Karnofsky Performance Status greater than or equal to 40.

You may not qualify if:

• Patients who meet any one of the following criteria will be excluded from study entry:
• Patients presenting with acute leukemia or bone marrow aspirate revealing greater than 10 percent blasts.
• Pregnant or lactating females (all patients must practice adequate birth control and females of child-bearing potential must have a negative serum beta-HCG pregnancy test (within Day -7 to Day 0).
• Acute infection: any acute viral, bacterial, or fungal infection which requires specific therapy. Acute therapy must have been completed within 14 days prior to study treatment.
• Hepatitis-B surface antigen positive patients.
• HIV-infected patients.
• Acute medical problems such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk.
• No patients with any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents used in this study).
• Patients less than 25 kg in weight .
• Patients who elect bone marrow transplantation.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Whitney MA, Saito H, Jakobs PM, Gibson RA, Moses RE, Grompe M. A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews. Nat Genet. 1993 Jun;4(2):202-5. doi: 10.1038/ng0693-202.

  PMID: 8348157 BACKGROUND

• Strathdee CA, Gavish H, Shannon WR, Buchwald M. Cloning of cDNAs for Fanconi's anaemia by functional complementation. Nature. 1992 Apr 30;356(6372):763-7. doi: 10.1038/356763a0.

  PMID: 1574115 BACKGROUND

• Strathdee CA, Duncan AM, Buchwald M. Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9. Nat Genet. 1992 Jun;1(3):196-8. doi: 10.1038/ng0692-196.

  PMID: 1303234 BACKGROUND

• Martinez-Balsalobre E, Guervilly JH, van Asbeck-van der Wijst J, Perez-Oliva AB, Lachaud C. Beyond current treatment of Fanconi Anemia: What do advances in cell and gene-based approaches offer? Blood Rev. 2023 Jul;60:101094. doi: 10.1016/j.blre.2023.101094. Epub 2023 Apr 28.

  PMID: 37142543 DERIVED

MeSH Terms

Conditions

Fanconi Anemia; Pancytopenia; Bone Marrow Failure Disorders

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Cytopenia

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: December 3, 1993
• Study Completion: February 11, 2009
• Last Updated: July 2, 2017

Record last verified: 2009-02-11

Locations

US (1)