Biological Therapy in Treating Patients With Primary or Advanced Glioma

Intracavitary Interleukin-2 (IL-2) and Lymphokine-Activated Killer (LAK) Cell Therapy for Malignant Gliomas

RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells in patients with primary or advanced glioma.

PURPOSE: Clinical trial to study the effectiveness of biological therapy with interleukin-2 and lymphokine-activated killer cells in treating patients who have primary, recurrent, or refractory malignant glioma.

OBJECTIVES:

• Confirm the antitumor efficacy of intracavitary interleukin-2 plus autologous lymphokine-activated killer cells in patients with primary, recurrent or refractory malignant gliomas.
• Determine whether the induction of a regional, intracavitary, eosinophilia is a prognosticator of response to immunotherapy and long term survival in these patients.

OUTLINE: Patients receive cytoreductive tumor surgery and/or biopsy and implantation of intracavitary Ommaya reservoir prior to therapy induction.

Patients undergo outpatient leukapheresis on day -4 or -5, and cells are incubated ex vivo with interleukin-2 (IL-2). Lymphokine-activated killer (LAK) cells and IL-2 are infused on day 1. Bolus infusions of low-dose IL-2 are administered on days 3, 5, 8, 10, and 12, followed by a rest period on days 13-24. The course is repeated on day 25 starting with leukapheresis. Therapy courses are repeated for up to 1 year for stable disease or response to therapy. Maintenance doses repeat every 4-6 months thereafter.

Disease restaging is done every 8-12 weeks.

PROJECTED ACCRUAL: A total of 30 patients per year will be enrolled.

DISEASE CHARACTERISTICS:

• Histologically or radiographically proven primary, recurrent, or refractory malignant gliomas (glioblastoma, anaplastic astrocytoma, and mixed anaplastic glioma)

  • Must be a candidate for neurosurgical biopsy or tumor debulking

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance Status:

• Karnofsky 60-100%

Life Expectancy:

• Greater than 4 months

Hematopoietic:

• Granulocytes greater than 1,500/mm^3
• Platelet count greater than 50,000/mm^3
• PT and PTT within normal limits

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal

Renal:

• Creatinine less than 1.5 mg/dL
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No congestive heart failure
• No coronary artery disease
• No serious cardiac arrhythmias
• No prior myocardial infarction

Pulmonary:

• No major pulmonary problems

Other:

• No history of neurologic disease (except related to brain tumor)
• No psychosis
• No impaired cognitive function
• No significant concurrent medical illness
• No active infection requiring antibiotic therapy
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• Adequate peripheral veins to permit leukapheresis, or placement of indwelling central vascular access device
• No hepatitis B or C
• HIV negative
• No prior autoimmune disease
• Allergy to gentamicin is allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 6 weeks since prior immunotherapy and recovered
• No concurrent immunotherapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for carmustine) and recovered
• No concurrent chemotherapy

Endocrine therapy:

• Reduction or elimination of corticosteroids
• Not greater than 0.15 mg/kg/day dexamethasone equivalent

Radiotherapy:

• At least 6 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• Prior surgery is allowed

Other:

• Concurrent therapy with acetaminophen, anticonvulsant agents, and headache pain medications is allowed