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
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
- 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.
- 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
- 18 and over
- Karnofsky 60-100%
- Greater than 2 months
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin greater than 10 g/dL
- Bilirubin no greater than 2.0 mg/dL
- ALT, AST, and alkaline phosphatase no greater than 2.5 times upper limit of normal
- Creatinine no greater than 2.0 times ULN
- 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:
- Not specified
- At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas)
- Concurrent steroid therapy allowed
- At least 4 weeks since prior radiotherapy
- Not specified