Vaccine Therapy in Treating Young Patients Who Are Undergoing Surgery for Malignant Glioma - Full Text View

Purpose

RATIONALE: Vaccines made from a person's white blood cells and tumor cells may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy after surgery may be a more effective treatment for malignant glioma.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating young patients who are undergoing surgery for malignant glioma.

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


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas in Pediatric Patients

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Glioma Oligodendroglioma Cerebral Astrocytoma, Childhood Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:

Dose-limiting toxicity of adjuvant vaccination with autologous tumor lysate-pulsed dendritic cells after surgical resection in pediatric patients with malignant glioma. [ Time Frame: 1 year ]

Secondary Outcome Measures:

survival [ Time Frame: 1 year ]
survival with this vaccine

Other Outcome Measures:

time to progression [ Time Frame: 1 year ]


Enrollment:	7
Study Start Date:	January 2005
Study Completion Date:	March 2010
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Vaccine	Biological: therapeutic autologous dendritic cells

Detailed Description:

OBJECTIVES:

Primary

Determine the dose-limiting toxicity of adjuvant vaccination with autologous tumor lysate-pulsed dendritic cells after surgical resection in pediatric patients with malignant glioma.
Determine the maximum tolerated dose of this vaccine in these patients.

Secondary

Determine, preliminarily, the survival of patients treated with this vaccine.
Determine, preliminarily, the time to tumor progression in patients treated with this vaccine.
Determine cellular immune response in patients treated with this vaccine.
Determine age-dependent differences in response to this vaccine, in terms of immunocompetence, in these patients.

OUTLINE: This is a dose-escalation study.

Patients undergo surgical resection to obtain tumor tissue for production of tumor lysate. Patients then undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMC) for generation of dendritic cells (DC). DC are pulsed with tumor lysate to produce an autologous dendritic cell vaccine. Approximately 10-30 days after leukapheresis, patients receive vaccination with autologous tumor lysate-pulsed dendritic cells intradermally on days 0, 14, and 28 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vaccine 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.

After completion of study treatment, patients are followed at 2 weeks and then every 2 months for 1 year.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 2-4.5 years.

Eligibility


Ages Eligible for Study:	1 Year to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed* WHO grade III or IV malignant glioma of 1 of the following subtypes:
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Glioblastoma multiforme NOTE: *Must be confirmed after surgery
Newly diagnosed OR recurrent disease
Bidimensionally measurable disease by contrast-enhancing pre-operative MRI
Surgically accessible tumor for which surgical resection is indicated at the time of initial pre-operative evaluation
Must have undergone standard surgery* AND either radiotherapy* or chemoradiotherapy*
Objective evidence of disease by contrast-enhanced brain MRI after completion of standard therapy NOTE: *Completed after study entry but before assignment to study treatment cohorts
Age 1 to 18
Performance status Karnofsky 60-100%
Hematopoietic
- Hemoglobin ≥ 10 g/dL
- Absolute granulocyte count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- SGPT and SGOT ≤ 2 times normal
- Alkaline phosphatase ≤ 2 times normal
- Bilirubin ≤ 1.5 mg/dL
- Hepatitis B and C negative
Renal
- BUN ≤ 1.5 times normal OR
- Creatinine ≤ 1.5 times normal
Immunologic
- HIV negative
- Syphilis negative
At least 2 weeks since prior radiotherapy and recovered
Negative pregnancy test
Fertile patients must use effective contraception
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
No chemotherapy during and for 4 weeks* after the final dose of study vaccine
No corticosteroids for at least 10 days before leukapheresis
No concurrent corticosteroids
More than 72 hours since prior systemic antibiotics
No antihistamines for 5 days before and for 5 days after administration of study vaccine

Exclusion Criteria:

history of immunodeficiency or 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
active infection
fever
allergy to study reagents
pregnant or nursing
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
unstable or severe medical or psychiatric condition, as determined by the investigator
underlying condition that would preclude study participation
concurrent radiotherapy
prior organ allograft
concurrent strong painkillers
other concurrent immune-suppressing medications
other concurrent investigational agents
other adjuvant treatment for 4 weeks* after the final dose of study vaccine NOTE: *Unless there is evidence of tumor progression necessitating additional clinically-indicated treatment; patients requiring treatment due to tumor progression are removed from the study

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00107185

Locations


United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781

Sponsors and Collaborators

Jonsson Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Joseph L. Lasky, MD	Jonsson Comprehensive Cancer Center

More Information


Responsible Party:	Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00107185 History of Changes
Other Study ID Numbers:	CDR0000420930 P30CA016042 ( U.S. NIH Grant/Contract ) UCLA-0410044-01
Study First Received:	April 5, 2005
Last Updated:	August 2, 2012

Keywords provided by Jonsson Comprehensive Cancer Center:


childhood high-grade cerebral astrocytoma recurrent childhood cerebral astrocytoma childhood oligodendroglioma

Additional relevant MeSH terms:


Glioma Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal	Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases

ClinicalTrials.gov processed this record on July 27, 2017