RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Inserting a specific gene into a person's peripheral stem cells may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus gene therapy in treating patients who have CNS tumors .

Condition	Treatment or Intervention	Phase
Brain Tumor	Drug: filgrastim  Drug: lomustine  Drug: procarbazine  Drug: vincristine	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the toxicity (detection of replication competent retrovirus) associated with CD34+ cells transduced with a retroviral vector expressing human O6-methylguanine DNA methyltransferase in adult and pediatric patients with poor prognosis CNS tumors. II. Determine the safety of genetic modification of cells carried out in the presence (ex vivo) of recombinant fibronectin (FN) fragment utilized to assist in retroviral entry into mammalian cells. III. Determine any evidence of engraftment of cells exposed to FN during retroviral transduction. IV. Determine any evidence of antibodies to FN following infusion of cells exposed to FN during ex vivo retroviral transduction.

PROTOCOL OUTLINE: Patients with surgically approachable lesions undergo maximal surgical debulking that allows preservation of good neurologic functioning. Harvest: Patients receive filgrastim (G-CSF) subcutaneously or IV beginning 4 days prior to initiation of first leukapheresis and continuing until completion of harvest. Peripheral blood stem cells are harvested and selected for CD34+ cells which are transduced with a fibronectin assisted retroviral vector expressing human O6-methylguanine DNA methyltransferase. Intensification: Patients receive oral lomustine and vincristine IV on day 0 and oral procarbazine on days 1-7. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with newly diagnosed tumors may undergo involved field radiotherapy (IF-RT) after completion of the third course of chemotherapy and may begin the fourth course of chemotherapy after completion of IF-RT. Transplantation: Two-thirds of the transduced CD34+ cells are reinfused on day 9 of the first course of chemotherapy. The remaining portion (one-third) of the transduced CD34+ cells are reinfused on day 9 of the second course of chemotherapy. Untransduced CD34+ cells are reinfused on day 9 of the last 3 courses of chemotherapy. Patients are followed every 3 months for 6 months, every 4 months for 1 year, every 6 months through year 5, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 15-20 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  5 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven newly diagnosed CNS tumors; Eligible tumor types: Glioblastoma multiforme (WHO grade IV); Anaplastic astrocytoma (WHO grade III); Anaplastic oligodendroglioma (WHO grade III); Mixed anaplastic oligoastrocytoma (WHO grade III); Incompletely resected ependymoma; Diffusely intrinsic pontine or medullary glioma Histology requirement waived OR Histologically proven recurrent or progressive CNS tumors; Eligible tumor types: Same as above plus oligodendroglioma (WHO grade II)
• No brainstem tumors arising from the cervicomedullary region or midbrain without histologic proof of malignancy
• No supratentorial low grade astrocytomas (WHO grade I or II)

--Prior/Concurrent Therapy--

• Biologic therapy: No growth factors after completion of study chemotherapy
• Chemotherapy: No prior nitrosourea or procarbazine
• Endocrine therapy: No concurrent dexamethasone as antiemetic
• Radiotherapy: No prior craniospinal radiotherapy
• Surgery: Not specified

--Patient Characteristics--

• Age: 5 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 2 months
• Hematopoietic: Absolute neutrophil count greater than 1,000/mm3; Platelet count greater than 100,000/mm3 (transfusion independent); Hemoglobin greater than 10 g/dL at time of pulmonary function testing
• Hepatic: Bilirubin less than 1.2 mg/dL; SGOT or SGPT less than 3 times normal
• Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance or radioisotope GFR greater than 70 mL/min
• Pulmonary: FEV1, FVC, and/or DLCO greater than 60% predicted; Children who are uncooperative with pulmonary function tests must have the following: No evidence of dyspnea at rest; No exercise intolerance; Oxygen saturation (by pulse oximetry) greater than 94% on room air
• Other: Minimum weight of 10 kg; Not pregnant or nursing; No active infection

Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5265,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States

Study chairs or principal investigators

James Croop,  Study Chair,  Indiana University Cancer Center   

Study ID Numbers:  CDR0000067758; IUMC-9607-22; NCI-H00-0049
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005796
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08