Protocol for a Phase I Study of Intrathecal LMB-7 (Single-Chain Immunotoxin Constructed From Monoclonal Antibody B3-Pseudomonas Exotoxin PE 38) [IND 5863, NSC 658931] in the Treatment of Patients With Leptomeningeal Neoplasms
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Protocol for a Phase I Study of Intrathecal LMB-7 (Single-Chain Immunotoxin Constructed From Monoclonal Antibody B3-Pseudomonas Exotoxin PE 38) [IND 5863, NSC 658931] in the Treatment of Patients With Leptomeningeal Neoplasms
OBJECTIVES: I. Determine the toxicity of intrathecal LMB-7 immunotoxin in patients with
leptomeningeal metastases. II. Identify objective therapeutic responses in this group of
patients.
OUTLINE: This is a dose escalation study. Patients receive LMB-7 intrathecally on days 1, 3,
and 5. Treatment may be repeated every 4 weeks if the patient does not demonstrate HAMA
neutralizing antibodies to PE-38 in CSF, has stable or responding disease, and has not
experienced greater than grade II toxicity. Three to six patients are entered at each dose
level. Dose escalation continues until the maximum tolerated dose (MTD) is determined. The
MTD is defined as the dose preceding that at which 2 of 6 patients experience grade 3 or
worse toxicity or a neuroradiology toxicity score of 10 or greater.
PROJECTED ACCRUAL: Approximately 15 to 24 patients will be accrued over one year.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically proven primary intracranial or extraneural
neoplasm with leptomeningeal metastases At least 30% of malignant cells in the
cerebrospinal fluid, primary tumor, or metastatic tumor must react with the B3 mouse
monoclonal antibody
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 50-100% Life
expectancy: Not specified Hematopoietic: ANC greater than 1000/mm3 Platelet count greater
than 100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL Renal: Creatinine less than 1.2
mg/dL Pulmonary: DLCO at least 60 Other: No neutralizing antibodies to Pseudomonas
exotoxin Not pregnant or nursing Not allergic to penicillin
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No chemotherapy
within past 4 weeks (6 weeks for nitrosoureas) unless there is evidence of disease
progression in CNS No concurrent chemotherapy Endocrine therapy: Patients receiving
corticosteroids must be on stable dose for 10 days prior to entry Radiotherapy: No
radiotherapy to disease site within past 3 months unless there is evidence of disease
progression in CNS No concurrent radiotherapy Surgery: Not specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Darell D. Bigner, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Duke Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000065605
NCT ID:
NCT00003020
Start Date:
September 1997
Completion Date:
September 2000
Related Keywords:
- Brain and Central Nervous System Tumors
- leptomeningeal metastases
- Neoplasm Metastasis
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Meningeal Neoplasms
- Meningeal Carcinomatosis
Name | Location |
|---|---|
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Kimmel Cancer Center of Thomas Jefferson University - Philadelphia | Philadelphia, Pennsylvania 19107 |
