Clinical trial NCT00836628 (phase 1, status: withdrawn)
Conditions: refractory brain tumors
ICD codes: D46.4, D46.1, D46.A, D46.0, D46.20, D46.21, D46.22
Drugs: busulfan
SMILES: CS(=O)(=O)OCCCCOS(C)(=O)=O
Reason stopped: 
    slow accrual
  
Eligibility criteria:

        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

        Exclusion Criteria:

          -  Pregnancy/Contraception: patients who are pregnant or breast-feeding will not be
             eligible.

          -  Patients of childbearing potential must practice an effective method of birth control
             while participating on the study.

          -  Females > 13 years of age or those who have achieved menarche must have a negative
             pregnancy test prior to study entry.