Lymphokine-Activated Killer Cells or Gliadel Wafer in Treating Patients With Newly Diagnosed Glioblastoma Multiforme That Can Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as lymphokine-activated killer cells, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as Gliadel wafer, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether lymphokine-activated killer cells are more effective than Gliadel wafer in treating patients with glioblastoma multiforme. PURPOSE: This randomized phase II trial is studying the side effects and how well lymphokine-activated killer cells work compared with Gliadel wafer in treating patients with newly diagnosed glioblastoma multiforme that can be removed by surgery.

Detailed Description
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OBJECTIVES: To compare the side effects, including infections and/or abnormal healing at the surgery site, associated with intralesional lymphokine-activated killer (LAK) cells vs polifeprosan 20 with carmustine implant (Gliadel® wafer) as consolidation therapy for patients with newly diagnosed resectable glioblastoma multiforme. To compare the overall survival of patients treated with these regimens. OUTLINE: Patients are stratified according to age (< 50 vs ≥ 50 years of age), Karnofsky performance status (70-80% vs 90-100%), use of corticosteroids > 4 mg/day (yes vs no), and progressive disease during first-line therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo intracranial placement of polifeprosan 20 with carmustine implant (Gliadel® wafer) at the time of therapeutic craniotomy. Arm II: Patients undergo leukapheresis to obtain autologous lymphokine-activated killer (LAK) cells, followed 3-7 days later by therapeutic craniotomy. The autologous LAK cells are then instilled into the tumor bed cavity at the time of therapeutic craniotomy. After completion of study treatment, patients are followed periodically for up to 5 years.

Official Title
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Randomized Phase II Trial of Intralesional Lymphokine Activated Killer Cells or Polifeprosan 20 With Carmustine Implant (Gliadel® Wafer) as Consolidation Therapy After Primary Treatment of Newly Diagnosed Resectable Glioblastoma

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: lymphokine-activated killer cells
* Drug: polifeprosan 20 with carmustine implant


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary malignant glioblastoma multiforme (GBM) (i.e., grade IV anaplastic astrocytoma) Must have undergone standard primary therapy (e.g., surgery, radiotherapy, and temozolomide) within the past 90 days Additional anticancer therapy as part of first-line therapy, including a radiosurgical procedure (e.g., stereotactic or gamma knife radiosurgery) allowed Must be an operable candidate and willing to undergo craniotomy PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% Life expectancy ≥ 2 months Hemoglobin > 10.0 g/dL AGC > 1,500/mm³ Platelet count > 100,000/mm³ Serum total bilirubin < 1.5 times upper limit of normal (ULN) ALT and AST < 2.5 times ULN Serum creatinine < 1.5 times ULN Negative pregnancy test Resides in the United States of America Venous access available for leukapheresis procedure to obtain peripheral blood mononuclear cells No diagnosis of any other invasive cancer within the past 5 years, except in situ carcinoma or basal cell carcinoma or localized squamous cell carcinoma of the skin Patients with prior diagnosis of minimal microscopic cancer (e.g., colonic polyp or stage I prostate cancer with Gleason score < 6) may be eligible, as determined by the principal investigator No concurrent serious medical or psychiatric illness that may interfere with giving informed consent or conducting this study No known hypersensitivity or allergy to either carmustine or aldesleukin PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 3 weeks since prior anticancer therapy and recovered No polifeprosan 20 with carmustine implant (Gliadel® wafer) at the time of prior surgery for GBM No prior treatment for progressive disease No other concurrent anticancer therapy (e.g., continuation of hormonal therapy for breast or prostate cancer that was diagnosed > 5 years ago)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients undergo intracranial placement of polifeprosan 20 with carmustine implant (Gliadel® wafer) at the time of therapeutic craniotomy. | Drug: polifeprosan 20 with carmustine implant<br>* Intracranial placement<br>|
| Experimental: Arm II<br>Patients undergo leukapheresis to obtain autologous lymphokine-activated killer (LAK) cells, followed 3-7 days later by therapeutic craniotomy. The autologous LAK cells are then instilled into the tumor bed cavity at the time of therapeutic craniotomy. | Biological: lymphokine-activated killer cells<br>* Instilled into the tumor bed cavity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years or death, whichever came first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of significant surgical wound infection (grade 3 or 4) |  | 4 weeks from date of study treatment. | 
| Rate of grade 3 or 4 non-infectious wound complications |  | 4 weeks from date of study treatment. | 
| Toxicity as assessed by NCI CTCAE version 3.0 |  | 4 weeks from date of study treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult giant cell glioblastoma, adult gliosarcoma, adult glioblastoma