Study of Busulfan for Refractory Central Nervous System (CNS) Tumors

Inclusion Criteria

• •Age: Age \>2 year and ≤ 21 years Histologic Diagnosis Any histological proven (confirmed by institutional pathology report; pathology slides from outside referring outside institutions are not required.) recurrent or progressive CNS tumor. (optic pathway and brainstem gliomas allowed without histologic verification, but must have diagnostic imaging).
• •Life Expectancy Patients must have a life expectancy of ≥ 2 months. Prior Therapy There is no limit to the number of prior therapies a patient has received
• •Must be ≥ 3 weeks from myelosuppressive chemotherapy (6 weeks from nitrosoureas) and have demonstrated recovery (ANC ≥ 1000/uL) from their last course of chemotherapy
• •≥ 6 months following allogeneic stem cell transplantation
• •≥ 3 months following autologous stem cell transplantation
• •≥ 3 months from craniospinal radiation
• •≥ 4 weeks from focal radiation
• •≥ 7 days from any past biologic/immunotherapy
• •≥ 1 week from any hematopoietic growth factors Concomitant Medication
• •Patients taking Itraconazole or Phenytoin will be excluded. Patients must be off of these medications for at least 3 days prior to entering this trial. If the patient is taking phenytoin for seizures at the time of study enrollment, it must be stopped at least 3 days prior to starting therapy and Clonazepam will be substituted during the Busulfex ® infusions and for 24 hours following the infusion.
• •Patients on growth stimulating factors, such as GCSF, will be allowed to continue these medications only as indicated in the study.
• •Patients may be taking steroids while participating in this trial, but should be on a stable dose for \>1 week prior to enrollment.
• •Medications interacting with the CYP3A4 substrate should also be avoided while the patient is on study.
• •Patients should also be on Pneumocystis prophylaxis while participating in this study. Pentamidine will be required, with a recommended dose of 4 mg/kg given intravenously every month. Pentamidine should continue throughout the duration of the trial.
• •Organ Function Requirements Adequate Bone Marrow Function Defined As
• •Peripheral absolute neutrophil count (ANC) greater than or equal to 1000/ul (off growth factors x 48 hrs)
• •Platelet count greater than or equal to 100,000/uL (transfusion independent)
• •Hemoglobin greater than or equal to 8.0 gm/dL (may receive RBC transfusions) Adequate Renal Function Defined As
• •Serum creatinine less than or equal to 1.5 x upper limit of normal, or
• •Estimated creatinine clearance GFR greater than or equal to 70 ml/min/1.73 m² by the Schwartz formula Adequate Liver Function Defined As
• •Total bilirubin within normal range
• •SGPT (ALT) within normal range Adequate Pulmonary Function Defined As
• •Oxygen saturation \>92% on room air Central Nervous System Function Defined As
• •Patients with seizure disorder may be enrolled; Patients MUST be on an anti-seizure medication upon enrollment, but this medication CANNOT be phenytoin or carbamezepine.
• •Patients must not be in status, coma or assisted ventilation prior to study enrollment.
• •Stable neurologic exam of at least 1 week duration Performance Level Karnofsky/ Lansky 50 or greater