Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas
OBJECTIVES:
- Determine the dose-limiting toxicity and maximum tolerated dose of autologous tumor
lysate-pulsed dendritic cells in patients with malignant gliomas.
- Determine survival, tumor progression, and cellular immune response in patients treated
with this regimen.
OUTLINE: This is a dose-escalation study.
Patients undergo leukapheresis for the collection of peripheral blood mononuclear cells
(PBMC). Autologous dendritic cells (DC) are prepared from autologous PBMC exposed to
sargramostim (GM-CSF) and interleukin-4 and pulsed with autologous tumor lysate. Patients
receive autologous tumor lysate-pulsed DC intradermally on days 0, 14, and 28 in the absence
of unacceptable toxicity.
Cohorts of 6-12 patients receive escalating doses of autologous tumor lysate-pulsed DC until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed every 2 months for 2 years.
PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 9-18
months.
Inclusion Criteria
Eligibility Criteria:
- Histologically confirmed diagnosis of one of the following malignant gliomas:
- Anaplastic astrocytoma
- Glioblastoma multiforme
- Anaplastic oligodendroglioma
- Malignant mixed oligoastrocytoma
- WHO grade III or IV disease
- Newly diagnosed disease
- Bidimensionally measurable disease by contrast-enhancing MRI
- Surgically accessible tumor for which resection is indicated
- Previously treated with or plan to undergo treatment with conventional external beam
radiotherapy
- Age 18 and over
- Performance status Karnofsky 60-100%
- Life expectancy at least 8 weeks
- Hemoglobin at least 10 g/dL
- Absolute granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- SGOT and SGPT no greater than 2 times normal
- Alkaline phosphatase no greater than 2 times normal
- Bilirubin no greater than 1.5 mg/dL
- Hepatitis B negative
- Hepatitis C negative
- BUN no greater than 1.5 times normal
- Creatinine no greater than 1.5 times normal
- HIV negative
- Syphilis serology negative
- Afebrile
- Negative pregnancy test
- Fertile patients must use effective contraception
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered.
- At least 2 weeks since prior corticosteroids
- At least 2 weeks since prior radiotherapy and recovered
- More than 72 hours since prior systemic antibiotics
Exclusion Criteria:
- active infection
- immunodeficiency
- autoimmune disease that may be exacerbated by immunotherapy, including any of the
following:
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Vasculitis
- Polymyositis-dermatomyositis
- Scleroderma
- Multiple sclerosis
- Juvenile-onset insulin-dependent diabetes
- allergy to study agents
- pregnant or nursing
- underlying condition that would contraindicate study therapy
- concurrent severe or unstable medical condition that would preclude giving informed
consent
- psychiatric condition that would preclude study participation or giving informed
consent
- other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, localized prostate cancer, or carcinoma in situ of the
cervix
- concurrent chemotherapy during and for 2 weeks after administration of study vaccine
- concurrent corticosteroids prior organ allograft
- antihistamine therapy within 5 days before or after administration of study vaccine
- other concurrent investigational agents
- concurrent adjuvant therapy during and for 2 weeks after administration of study
vaccine
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose Limiting Toxicity
Outcome Time Frame:
4 weeks
Safety Issue:
Yes
Principal Investigator
Linda M. Liau, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000327711
NCT ID:
NCT00068510
Start Date:
June 2003
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- adult glioblastoma
- adult anaplastic astrocytoma
- adult brain tumor
- adult giant cell glioblastoma
- adult gliosarcoma
- adult anaplastic oligodendroglioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Glioma
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center at UCLA | Los Angeles, California 90095-1781 |
