Vaccine Therapy in Treating Patients With Malignant Glioma

• ClinicalTrials.gov Identifier: NCT00068510
• Recruitment Status: Completed
• First Posted: September 11, 2003
• Last Update Posted: August 3, 2020
• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): Jonsson Comprehensive Cancer Center

Tracking Information

• First Submitted Date: September 10, 2003
• First Posted Date: September 11, 2003
• Last Update Posted Date: August 3, 2020
• Study Start Date: June 2003
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 13, 2012): Dose Limiting Toxicity [ Time Frame: 4 weeks ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: June 13, 2012): Time to tumor progression, overall survival and cellular immune responses in brain tumor patients injected with tumor lysate pulsed dendritic cells [ Time Frame: 2 years ]
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vaccine Therapy in Treating Patients With Malignant Glioma
• Official Title: Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas

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.

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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Brain and Central Nervous System Tumors
• Intervention: Biological: therapeutic autologous dendritic cells

Study Arms

Experimental: autologous tumor lysate-pulsed DC

Intervention: Biological: therapeutic autologous dendritic cells

Publications *

• Liau LM, Prins RM, Kiertscher SM, Odesa SK, Kremen TJ, Giovannone AJ, Lin JW, Chute DJ, Mischel PS, Cloughesy TF, Roth MD. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 2005 Aug 1;11(15):5515-25.
• Prins RM, Wang X, Soto H, Young E, Lisiero DN, Fong B, Everson R, Yong WH, Lai A, Li G, Cloughesy TF, Liau LM. Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. J Immunother. 2013 Feb;36(2):152-7. doi: 10.1097/CJI.0b013e3182811ae4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 22, 2013): 28
• Original Enrollment: Not Provided
• Actual Study Completion Date: September 2012
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00068510
• Other Study ID Numbers: CDR0000327711; UCLA-0304053
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Jonsson Comprehensive Cancer Center
• Study Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Institutes of Health (NIH)

Investigators

• Principal Investigator: Linda M. Liau, MD, PhD; Jonsson Comprehensive Cancer Center

• PRS Account: Jonsson Comprehensive Cancer Center
• Verification Date: August 2013