Vaccine Therapy in Treating Patients With Malignant Glioma

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00068510

Collaborator

National Institutes of Health (NIH) (NIH)

Enrollment

Location

Arm

111

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with malignant glioma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Biological: therapeutic autologous dendritic cells	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas

Study Start Date :

Jun 1, 2003

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: autologous tumor lysate-pulsed DC	Biological: therapeutic autologous dendritic cells

Arm

Intervention/Treatment

Experimental: autologous tumor lysate-pulsed DC

Biological: therapeutic autologous dendritic cells

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity [4 weeks]

Secondary Outcome Measures

Time to tumor progression, overall survival and cellular immune responses in brain tumor patients injected with tumor lysate pulsed dendritic cells [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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