Vaccine Therapy in Treating Young Patients Who Are Undergoing Surgery for Malignant Glioma

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00107185

Collaborator

(none)

Enrollment

Location

Arm

61.9

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

7 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 in Pediatric Patients

Study Start Date :

Jan 1, 2005

Actual Primary Completion Date :

Oct 1, 2009

Actual Study Completion Date :

Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vaccine	Biological: therapeutic autologous dendritic cells

Arm

Intervention/Treatment

Experimental: Vaccine

Biological: therapeutic autologous dendritic cells

Outcome Measures

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. [1 year]

Secondary Outcome Measures

survival [1 year]
survival with this vaccine

Other Outcome Measures

time to progression [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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