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

Dartmouth Health

Status and phase: Completed; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Biological: lymphokine-activated killer cells; Biological: bispecific antibody MDX447; Procedure: conventional surgery

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00005813

NCI-G00-1783 (Other Grant/Funding Number)

D9705

P30CA023108 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

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