Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
OBJECTIVES: I. Compare the rate of treatment failure in osteopetrosis patients receiving
 interferon gamma in combination with calcitriol to the rate of treatment failure in patients
 receiving calcitriol alone.

 II. Compare the number of adverse events or clinical manifestations of disease progression
 occurring in these patients.

 III. Assess the effects of interferon gamma on hematopoiesis, cranial nerve function, and
 rate of infection in these patients.
PROTOCOL OUTLINE: This is a randomized, placebo controlled, open label study. Patients are
 randomized to one of two arms (interferon gamma in combination with calcitriol or calcitriol
 alone).

 Arm I: Patients receive calcitriol once daily. Interferon gamma is administered by
 subcutaneous injection three times a week.

 Arm II: Patients receive calcitriol once daily. Patients may continue treatment in the
 absence of toxicity and disease progression. If disease progression is diagnosed in the
 control group, patients will then receive interferon gamma in combination with calcitriol.

 Patients are followed every 4 weeks.
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 -  Biopsy and x-ray confirmed primary osteopetrosis

 -  Presence of anemia and/or cranial nerve compression

 --Prior/Concurrent Therapy--

 -  Biologic therapy: No prior/concurrent bone marrow transplantation No prior interferon
 gamma No other investigational biologic agents

 -  Chemotherapy: No prior/concurrent chemotherapeutic agents for bone marrow
 transplantation

 -  Endocrine therapy: Prior/concurrent corticosteroid as supportive therapy allowed

 -  Radiotherapy: Not specified

 -  Surgery: At least 5 days since major surgery

 -  Other: Prior/concurrent calcitriol as supportive therapy allowed Prior/concurrent
 transfusion as supportive therapy allowed Prior/concurrent dietary therapy allowed

 --Patient Characteristics--

 -  Age: 2 months to 10 years

 -  Performance status: Not specified

 -  Life expectancy: At least 6 months

 -  Hematopoietic: Not specified

 -  Hepatic: Bilirubin less than 2 mg/dL

 -  Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance greater than 50 mL/min

 -  Pulmonary: No uncorrected airway obstruction

 -  Other: No active infection requiring intravenous antibiotics No known seizure disorder
 not related to hypocalcemia No uncorrected hydrocephalus No MRI evidence of cerebral
 atrophy Must maintain or gain body weight No sleep apnea No thrombocytopenia No
 massive splenomegaly