RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Vaccines made from a person's white blood cells and tumor cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and vaccine therapy followed by bone marrow or peripheral stem cell transplantation and interleukin-2 in treating patients who have recurrent or refractory brain cancer.

Condition	Treatment or Intervention	Phase
Brain Tumor	Drug: autologous lymphocytes  Drug: autologous tumor cell vaccine  Drug: carmustine  Drug: cisplatin  Drug: cyclophosphamide  Drug: filgrastim  Drug: interleukin-2  Drug: paclitaxel  Drug: sargramostim	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the effectiveness of induction paclitaxel and cyclophosphamide followed by autologous tumor cell vaccine and sargramostim (GM-CSF) followed by high-dose chemotherapy with cisplatin, cyclophosphamide, and carmustine, autologous bone marrow or peripheral blood stem cell transplantation, and interleukin-2 in patients with recurrent or refractory primary high-grade brain tumors. II. Determine the safety and toxicity of this regimen in these patients. III. Determine if a specific quantitative cellular response can be elicited in patients treated with this regimen.

PROTOCOL OUTLINE: After partial surgical resection of tumor, patients receive induction chemotherapy comprising paclitaxel IV over 3 hours and cyclophosphamide IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 3 and continuing until peripheral blood stem cell (PBSC) or bone marrow collection is completed. After the collection of PBSC or bone marrow, patients receive autologous tumor cell vaccine and sargramostim (GM-CSF) SC once every 2 weeks for up to 5 vaccinations. Two weeks after the last vaccination, patients undergo a second leukapheresis to collect lymphocytes. After completion of the second leukapheresis, patients receive high-dose chemotherapy comprising cisplatin IV continuously over 24 hours on day -5, cyclophosphamide IV over 1 hour on days -5, -4, and -3, and carmustine IV over 2 hours on day -2. Patients undergo autologous bone marrow or PBSC transplantation on day 0. Patients receive G-CSF IV daily beginning on day 0 and continuing until blood counts recover. Approximately 12 weeks after bone marrow or PBSC transplantation, patients receive autologous lymphocytes IV over 2-5 hours. Patients also receive interleukin-2 IV once every other day for 10 days. Patients are followed at 18, 24, 36, 40, and 52 weeks.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Ages Eligible for Study:  up to  65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed active recurrent or refractory primary high-grade brain tumor; Tumor must be surgically accessible
• Bidimensionally measurable disease by clinical exam, CT scan, or x-ray; Disease must be outside a previously irradiated field or have progressed or developed after radiotherapy; Previously treated metastatic bony lesions are not considered measurable
• No previously irradiated metastatic disease site unless no response or clear progression on imaging

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: Recovered from prior conventional chemotherapy
• Endocrine therapy: No concurrent steroid therapy for mass effect
• Radiotherapy: See Disease Characteristics; Recovered from prior conventional radiotherapy
• Surgery: See Disease Characteristics

--Patient Characteristics--

• Age: 65 and under
• Performance status: CALGB 0-2
• Life expectancy: More than 3 months
• Hematopoietic: Absolute neutrophil count greater than 1,500/mm3; Platelet count greater than 100,000/mm3
• Hepatic: Liver function less than 2.5 times normal unless due to disease; No active hepatitis B or C
• Renal: Creatinine less than 1.5 mg/dL; Creatinine clearance greater than 60 mL/min
• Cardiovascular: Left ventricular ejection fraction greater than 50% by MUGA or 2-D echocardiogram; Electrocardiogram normal
• Pulmonary: FEV1 and DLCO greater than 50% predicted OR Clearance by pulmonologist
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; HIV negative; No serious underlying co-morbid disease or other medical or psychiatric factor that would preclude study; Able to be weaned off steroids after surgery

Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States

Study chairs or principal investigators

Esteban Abella,  Study Chair,  Barbara Ann Karmanos Cancer Institute   

Study ID Numbers:  CDR0000068559; WSU-D-1654; NCI-G01-1937; WSU-07-92-98-P04-FB
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  April 10, 2001
ClinicalTrials.gov Identifier:  NCT00014573
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08