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

• ClinicalTrials.gov Identifier: NCT00107185
• Recruitment Status: Completed
• First Posted: April 6, 2005
• Last Update Posted: August 5, 2020
• Sponsor: Jonsson Comprehensive Cancer Center
• Information provided by (Responsible Party): Jonsson Comprehensive Cancer Center

Tracking Information

• First Submitted Date: April 5, 2005
• First Posted Date: April 6, 2005
• Last Update Posted Date: August 5, 2020
• Study Start Date: January 2005
• Actual Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 2, 2012): 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 ]
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: August 2, 2012)

survival [ Time Frame: 1 year ]

survival with this vaccine

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures (submitted: August 2, 2012): time to progression [ Time Frame: 1 year ]
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

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 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: Vaccine

Intervention: Biological: therapeutic autologous dendritic cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 2, 2012): 7
• Original Enrollment: Not Provided
• Actual Study Completion Date: March 2010
• Actual Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 18 Years (Child, 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: NCT00107185
• Other Study ID Numbers: CDR0000420930; UCLA-0410044-01
• 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: Not Provided

Investigators

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

• PRS Account: Jonsson Comprehensive Cancer Center
• Verification Date: August 2012