Pilot Study of Etanercept (Enbrel) in Children With Fanconi Anemia

Inclusion Criteria:

1. Patients must have a diagnosis of FA proven by a DEB test conducted in the cytogenetics lab of Dr. Arleen Auerbach, Rockefeller University Hospital.
2. Patients must have evidence of early marrow failure i.e. reduction in at least one cell line on two separate occasions at least one month apart e.g. platelet count of < 100,000 per cubic millimeter, hemoglobin < 9 gm/dl and/or absolute neutrophil count (ANC) of < 1000
3. Negative pregnancy test (conducted via serum β-HCG screen) - done before the first dose of study drug in all women (except those surgically sterile, at least 5 years postmenopausal, or under the age of 10 years)
4. Sexually active patients of childbearing potential must agree to use medically acceptable form of contraception during screening and throughout the study
5. Patients or designees must have the ability to self-inject investigational product or have a care giver at home who can administer subcutaneous injections
6. Patients or designees must be able and willing to give written informed consent and comply with the requirements of the study protocol and must authorize release and use of protected health information
7. Patients must have a negative TB skin test at entry into the study

Exclusion Criteria:

1. Patients < 4 yrs of age
2. Patients with advanced marrow failure i.e. transfusion dependent, will not be eligible as we anticipate that stem cell depletion will already be advanced at this stage.
3. Patients currently enrolled in another investigational device or drug trial(s) (defined as a drug not approved by the FDA), or who have received other investigational agent(s) within 28 days of baseline visit with the exception of CCHMC IRB protocol # 03-9-11, "Thyroid Hormone in Children with Fanconi Anemia"
4. Patients on androgen therapy
5. Patients who have received immunosuppressive agents within the last 3 months prior to enrollment
6. Patients who have any grade 3 or 4 adverse event or laboratory toxicity other than in Blood or Bone Marrow (as per the NCI CTC criteria) at the time of the screening visit or at any time during the study, that in the opinion of the Investigator would preclude participation in the study
7. Patients with active infections within 4 weeks before the screening/baseline visit
8. Patients with untreated Lyme disease
9. Patients with a recent or past history of fungal infection
10. Patients who have history of TB or TB exposure, chronic hepatitis B or hepatitis C, SLE, history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy
11. Patients with known hypersensitivity to Etanercept (Enbrel) or any of its components or who are known to have antibodies to Etanercept (Enbrel).
12. Patients who have received hematopoietic growth factor for greater than 3 consecutive days in the 6 months before study enrollment (i.e., erythropoietin, filgrastim, neupogen, sargramostin) for clinical purposes to improve bone marrow function. Patients receiving hematopoietic growth factor for stem cell mobilization and collection only are not excluded from this study.
13. Patients with an available matched sibling donor and clinically indicated need for bone marrow transplant
14. Patients with renal failure requiring dialysis
15. Patients with a total bilirubin >3 mg/dl and/or SGPT >200 at time of enrollment
16. Patients who are pregnant or breastfeeding or are a female at risk of pregnancy and are unable to practice safe sex during the length of the study
17. Patients who are HIV positive
18. Patients with severe co-morbidities (diabetes mellitus requiring insulin, CHF of any severity, MI, CVA or TIA within 3 months of screening visit, unstable angina pectoris, uncontrolled hypertension, oxygen-dependent severe pulmonary disease, history of cancer within 5 years (other than resected cutaneous basal or squamous cell carcinoma or in situ cervical cancer)
19. Patients who have any mycobacterial disease or known history of any other immuno-suppressing disease
20. Patients with a history of recent alcohol or substance abuse (< 1 year)
21. Patients with a history of non-compliance with other therapies
22. Patients who have any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient