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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00107185
First received: April 5, 2005
Last updated: August 2, 2012
Last verified: August 2012

April 5, 2005
August 2, 2012
January 2005
October 2009   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00107185 on ClinicalTrials.gov Archive Site
survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
survival with this vaccine
Not Provided
time to progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Not Provided
 
Vaccine Therapy in Treating Young Patients Who Are Undergoing Surgery for Malignant Glioma
Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas in Pediatric Patients

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
Biological: therapeutic autologous dendritic cells
Experimental: Vaccine
Intervention: Biological: therapeutic autologous dendritic cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
7
March 2010
October 2009   (final data collection date for primary outcome measure)

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
Both
1 Year to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00107185
CDR0000420930, P30CA016042, UCLA-0410044-01
Yes
Jonsson Comprehensive Cancer Center
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Joseph L. Lasky, MD Jonsson Comprehensive Cancer Center
Jonsson Comprehensive Cancer Center
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP