Dendritic Cell Vaccine for Patients With Brain Tumors

• ClinicalTrials.gov Identifier: NCT01204684
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2010
• Last Update Posted: February 28, 2020
• Sponsor: Jonsson Comprehensive Cancer Center
• Information provided by (Responsible Party): Jonsson Comprehensive Cancer Center

Tracking Information

• First Submitted Date: September 16, 2010
• First Posted Date: September 17, 2010
• Last Update Posted Date: February 28, 2020
• Actual Study Start Date: October 8, 2010
• Estimated Primary Completion Date: January 31, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 7, 2013): Most effective combination of DC vaccine components [ Time Frame: 6 weeks ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: January 7, 2013): Time to tumor progression and overall survival [ 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: Dendritic Cell Vaccine for Patients With Brain Tumors
• Official Title: A Phase II Clinical Trial Evaluating Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen +/- Toll-like Receptor Agonists for the Treatment of Malignant Glioma
• Brief Summary: The main purpose of this study is to evaluate the most effective immunotherapy vaccine components in patients with malignant glioma. Teh investigators previous phase I study (IRB #03-04-053) already confirmed that this vaccine procedure is safe in patients with malignant brain tumors, and with an indication of extended survival in several patients. However, the previous trial design did not allow us to test which formulation of the vaccine was the most effective. This phase II study will attempt to dissect out which components are most effective together. Dendritic cells (DC) (cells which "present" or "show" cell identifiers to the immune system) isolated from the subject's own blood will be treated with tumor-cell lysate isolated from tumor tissue taken from the same subject during surgery. This pulsing (combining) of antigen-presenting and tumor lysate will be done to try to stimulate the immune system to recognize and destroy the patient's intracranial brain tumor. These pulsed DCs will then be injected back into the patient intradermally as a vaccine. The investigators will also utilize adjuvant imiquimod or poly ICLC (interstitial Cajal-like cell) in some treatment cohorts. It is thought that the host immune system might be taught to "recognize" the malignant brain tumor cells as "foreign" to the body by effectively presenting unique tumor antigens to the host immune cells (T-cells) in vivo.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Glioma
• Anaplastic Astrocytoma
• Anaplastic Astro-oligodendroglioma
• Glioblastoma

Intervention

• Biological: autologous tumor lysate-pulsed DC vaccination
• Biological: Tumor lysate-pulsed DC vaccination+0.2% resiquimod
• Biological: Tumor-lysate pulsed DC vaccination +adjuvant polyICLC

Study Arms

• Experimental: Tumor Lysate-pulsed DC vaccination
  Cohort #1 will receive autologous tumor lysate-pulsed DC vaccination together with a placebo cream or intramuscular injection of saline.
  Intervention: Biological: autologous tumor lysate-pulsed DC vaccination
• Experimental: Tumor lysate-pulsed DC vaccination+0.2% resiquimod.
  Cohort #2 will receive autologous tumor lysate-pulsed DC vaccination together with adjuvant 0.2% resiquimod.
  Intervention: Biological: Tumor lysate-pulsed DC vaccination+0.2% resiquimod
• Experimental: Tumor-lysate pulsed DC vaccination +adjuvant polyICLC.
  Cohort #3 will receive autologous tumor lysate-pulsed DC vaccination together with adjuvant poly ICLC (TLR3 agonist).
  Intervention: Biological: Tumor-lysate pulsed DC vaccination +adjuvant polyICLC

Publications *

• Liau LM, Black KL, Prins RM, Sykes SN, DiPatre PL, Cloughesy TF, Becker DP, Bronstein JM. Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg. 1999 Jun;90(6):1115-24.
• 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, Liau LM. Cellular immunity and immunotherapy of brain tumors. Front Biosci. 2004 Sep 1;9:3124-36. Review.
• Prins RM, Cloughesy TF, Liau LM. Cytomegalovirus immunity after vaccination with autologous glioblastoma lysate. N Engl J Med. 2008 Jul 31;359(5):539-41. doi: 10.1056/NEJMc0804818.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 7, 2013): 60
• Original Enrollment: Not Provided
• Estimated Study Completion Date: January 31, 2022
• Estimated Primary Completion Date: January 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

PATIENT ELIGIBILITY

Inclusion Criteria

1. Patients with newly diagnosed or recurrent glioma of WHO Grade III or IV {anaplastic astrocytoma (AA), anaplastic astro-oligodendroglioma (AO), or glioblastoma (GBM)} will be eligible for this protocol.
2. Patients must have had surgical resection at UCLA (University of California, Los Angeles), for which a separate informed consent was signed for the collection of their tumor prior to surgery.
3. After surgery, a pathological diagnosis of malignant glioma (WHO Grade III or IV) will need to be established.
4. Patients must be 18 years or older and able to read and understand the informed consent document. Patients must sign the informed consent indicating that they are aware of the investigational nature of this study.
5. Patients must have a Karnofsky performance status (KPS) rating of > 60 prior to initiating treatment. Patients may be enrolled at a KPS of < 60 if it is felt that the patient will have adequate opportunity to recover to a KPS of > 60 by the initiation of treatment.

Exclusion Criteria

1. Subjects with an active infection.
2. Inability to obtain informed consent because of psychiatric or complicating medical problems.
3. Unstable or severe intercurrent medical or psychiatric conditions as determined by the Investigator.
4. Females of child-bearing potential who are pregnant or lactating or who are not using approved contraception.
5. History of immunodeficiency (e.g., HIV) or autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, vasculitis, polymyositis-dermatomyositis, scleroderma, multiple sclerosis, or juvenile-onset insulin-dependent diabetes) that may be exacerbated by immunotherapy.
6. Subjects with organ allografts.
7. Inability or unwillingness to return for required visits and follow-up exams.
8. Subjects who have an uncontrolled systemic malignancy that is not in remission.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (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: NCT01204684
• Other Study ID Numbers: 10-000202
• 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: Not Provided
• PRS Account: Jonsson Comprehensive Cancer Center
• Verification Date: February 2020