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

• Status: Completed
• Trial end date: 2009-02-11
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

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

Criteria

• INCLUSION CRITERIA:

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.

Although there are no blood count criteria for inclusion in this study, preference will be given to patients with significant marrow failure as reflected by anemia, neutropenia, and/or thrombocytopenia. Furthermore, we intend to first enroll adults and older children, to the extent possible, before enrolling younger children.

EXCLUSION CRITERIA:

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.