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.

Condition	Treatment or Intervention	Phase
adult glioblastoma multiforme	Procedure: biological response modifier therapy  Procedure: surgery  Procedure: monoclonal antibody therapy  Procedure: antibody therapy  Procedure: leukocyte therapy  Procedure: lymphokine-activated killer cell therapy  Procedure: conventional surgery  Drug: bispecific antibody MDX447  Drug: bispecific antibody MDX447/lymphokine-activated killer cells  Drug: lymphokine-activated killer cells	Phase I

Further Study Details: 

OBJECTIVES: I. Assess the safety and tolerability of bispecific antibody MDX447 and activated monocytes in patients with recurrent or refractory glioblastoma multiforme. II. Determine the response, time to tumor progression, and overall survival of these patients treated with this regimen.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%
• Life expectancy: Greater than 2 months
• Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 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

New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States

Study chairs or principal investigators

Camilo E. Fadul,  Study Chair,  Norris Cotton Cancer Center   

Study ID Numbers:  CDR0000067815; DMS-9705; NCI-G00-1783
Record last reviewed:  August 2003
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005813
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08