Bispecific Antibody Plus White Blood Cells in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme

Study Overview
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Brief Summary
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RATIONALE: Bispecific antibodies plus white blood cells may be able to locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of combining bispecific antibodies with white blood cells in treating patients who have recurrent or refractory glioblastoma multiforme.

Detailed Description
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OBJECTIVES: Assess the safety and tolerability of bispecific antibody MDX447 and activated monocytes in patients with recurrent or refractory glioblastoma multiforme. Determine the response, time to tumor progression, and overall survival of these patients treated with this regimen. OUTLINE: This is a dose escalation study. Patients undergo maximal surgical debulking of the tumor at the time of reservoir placement. Within 2-4 weeks after surgery, patients receive one treatment of intratumoral bispecific antibody MDX447 and activated monocytes. Stable or responding patients may receive a second treatment 1 month later. Cohorts of 1 or 3 patients receive escalating doses of bispecific antibody MDX447 and activated monocytes until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 patients experience dose limiting toxicities. PROJECTED ACCRUAL: A total of 13 patients will be accrued for this study.

Official Title
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A Phase I Trial of Intratumoral Bispecific Antibody and Activated Monocytes in Patients With Recurrent or Refractory Glioblastoma Multiforme

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: bispecific antibody MDX447
* Biological: lymphokine-activated killer cells
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven glioblastoma multiforme with evidence of epidermal growth factor receptor (EGFR) expression on tumor cell surfaces No astrocytoma, anaplastic astrocytoma, or oligodendroglioma No infratentorial or multifocal tumor Recurrence or progression following at least one prior therapy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Greater than 2 months Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin greater than 10 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL ALT, AST, and alkaline phosphatase no greater than 2.5 times upper limit of normal (ULN) Renal: Creatinine no greater than 2.0 times ULN Other: Not pregnant or nursing Fertile patients must use effective contraception No other medical or psychiatric illness that would preclude study No other concurrent malignancy except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas) Endocrine therapy: Concurrent steroid therapy allowed Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: Not specified

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bispecific antibody MDX447|nan|
|Biological: lymphokine-activated killer cells|nan|
|Procedure: conventional surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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