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Phase I Study of a Dendritic Cell Vaccine for Patients With Either Newly Diagnosed or Recurrent Glioblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Cedars-Sinai Medical Center
Sponsor:
Information provided by (Responsible Party):
Jethro Hu, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT02010606
First received: December 2, 2013
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to test the safety and effects of a special type of a cancer vaccine called a 'dendritic cell vaccine' in patients with either newly diagnosed or recurrent glioblastoma. The goal of this dendritic cell vaccine is to activate a patient's own immune system against their tumor. This study utilizes a patient's own immune-stimulating dendritic cells that are isolated in a procedure called leukapheresis. In a laboratory, these dendritic cells are treated in a way that is designed to promote an immune response against cancer stem cells. Then the dendritic cells are injected under the skin in a series of vaccinations, with the goal of activating an immune response against cancer stem cells in the tumor.

To qualify for this study, patients must have very little to no residual tumor visible on a recent MRI. In addition to the vaccines, patients with newly diagnosed glioblastoma will receive standard temozolomide chemotherapy and radiation therapy. Patients with recurrent glioblastoma will not receive any treatment other than the vaccines as long as they are participating in this study, unless they were previously treated with bevacizumab, in which case they will be allowed to continue receiving bevacizumab.


Condition Intervention Phase
Glioblastoma
Glioblastoma Multiforme
Glioma
Astrocytoma
Brain Tumor
Biological: Dendritic cell vaccination, in addition to standard temozolomide chemotherapy and involved field radiation therapy
Biological: Dendritic cell vaccination, with optional bevacizumab treatment for patients previously treated with bevacizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Vaccination With Autologous Dendritic Cells Pulsed With Lysate Derived From an Allogeneic Glioblastoma Stem-like Cell Line for Patients With Newly Diagnosed or Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • Assess safety and tolerability according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAEs) Version 4.03 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Assess the number of serious adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Assess treatment-related toxicities [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    We will assess possible vaccine-related adverse effects, including but not limited to cerebral edema, autoimmune reactions, and allergic reactions.


Secondary Outcome Measures:
  • Evaluate Overall Survival (OS) and Progression-Free Survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Evaluate health-related quality of life parameters [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Assess the overall response rate, defined as the percentage of patients showing either partial response or complete response, in patients with subtotal resection [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Evaluate immune response by assessing cytotoxic T cell activity in vitro pre- vs post-vaccination [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2013
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A: Patients with newly diagnosed glioblastoma
Dendritic cell vaccination, in addition to standard temozolomide chemotherapy and involved field radiation therapy
Biological: Dendritic cell vaccination, in addition to standard temozolomide chemotherapy and involved field radiation therapy
Patients will receive a series of four vaccines given weekly during the Induction phase, followed by vaccinations every 8 weeks during the Maintenance phase for as long as patients remain on the study or until the vaccine supply is depleted. In addition to the investigative treatment, patients with newly diagnosed glioblastoma will receive standard temozolomide chemotherapy and radiation treatment, with the vaccine Induction phase beginning at the conclusion of radiation.
Experimental: Cohort B: Patients with recurrent glioblastoma
Dendritic cell vaccination, with optional bevacizumab treatment for patients previously treated with bevacizumab
Biological: Dendritic cell vaccination, with optional bevacizumab treatment for patients previously treated with bevacizumab
Patients will receive a series of four vaccines given weekly during the Induction phase, followed by vaccinations every 8 weeks during the Maintenance phase for as long as patients remain on the study or until the vaccine supply is depleted. Patients with recurrent glioblastoma will not receive additional treatment other than the investigative treatment as long as they remain on study, unless they were previously treated with bevacizumab, in which case they will be allowed to continue receiving bevacizumab

Detailed Description:

This phase I study for patients with either newly diagnosed or recurrent glioblastoma with minimal residual tumor utilizes a dendritic cell vaccine consisting of autologous dendritic cells that have been pulsed with a lysate derived from an allogeneic glioblastoma stem-like cell line cultured under neurosphere-forming conditions.

Patients will receive a series of four vaccines given weekly during the Induction phase, followed by vaccinations every 8 weeks during the Maintenance phase for as long as patients remain on the study or until the vaccine supply is depleted. In addition to the investigative treatment, patients with newly diagnosed glioblastoma will receive standard temozolomide chemotherapy and radiation treatment, with the Induction phase beginning at the conclusion of radiation. Patients with recurrent glioblastoma will not receive treatment other than the investigative treatment, unless they were previously treated with bevacizumab, in which case they will be allowed to continue receiving bevacizumab.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed glioblastoma (Cohort A), or glioblastoma at first-third recurrence (Cohort B). Patients with an initial biopsy or partial resection can qualify for Cohort A if the second surgery (to achieve gross total resection) occurs within 30 days of the initial surgery, without any interval treatment using radiation or chemotherapy between the two surgeries. To qualify for Cohort B, patients must have previously been treated with involved-field radiation therapy with concurrent temozolomide chemotherapy, and pathology from the resection that qualifies the patient for the trial must be consistent with recurrent disease (ie, patients with predominantly pseudoprogression or radiation necrosis are not eligible). Patients with recurrent glioblastoma are eligible up to and including third recurrence, and therefore are permitted to have been treated with up to three distinct chemotherapy regimens prior to trial enrollment. Prior bevacizumab therapy is allowed for patients in Cohort B. Patients with secondary glioblastoma (ie, patients who were initially diagnosed with lower grade gliomas) who were treated with radiation and temozolomide prior to resection in which transformation to glioblastoma was noted are also eligible for Cohort B.
  • Complete resection of tumor: gross total resection consisting of no gadolinium enhancement or linear gadolinium enhancement along the resection cavity; or subtotal resection consisting of linear enhancement with nodular gadolinium enhancement of less than 1cm x 1cm x 1cm total volume
  • ≥ 18 years of age
  • Karnofsky Performance Score (KPS) of ≥ 70%
  • Baseline hematologic studies and chemistry profiles must meet the following criteria: hemoglobin (Hgb) > 9.9 g/dL, absolute neutrophil count (ANC) > 1000/mm3, platelet count > 100,000/mm3, blood urea nitrogen (BUN) < 30 mg/dL, creatinine < 1.4 mg/dL, alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 4x upper limit of normal (ULN), prothrombin time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6 x control unless therapeutically warranted
  • Female patients of child bearing potential must have negative serum pregnancy test
  • If not surgically sterile, male and female patients of childbearing age must use double barrier contraception (hormonal; intrauterine device; barrier)
  • Written informed consent, Release of Medical Records Form and HIPAA reviewed and signed by patient or legally authorized representatives
  • Ability to understand and the willingness to sign a written informed consent document.
  • Any Grade 3 or 4 toxicities (according to NCI CTCAE) resolved for at least 2 weeks to Grade 1 or less

Exclusion Criteria:

  • Prior placement of intracavitary BCNU-impregnated wafers (Gliadel), as this treatment can result in an inflammatory reaction that mimics disease progression radiographically.
  • Presence of any other active malignancy or prior history of malignancy, except for: basal cell carcinoma of the skin, cervical carcinoma in situ, early stage prostate carcinoma not requiring active treatment
  • Severe pulmonary, cardiac or other systemic disease, specifically:
  • New York Heart Association > Grade 2 congestive heart failure within 6 months prior to study entry
  • Uncontrolled or significant cardiovascular disease, including: myocardial infarction and transient ischemic attack or stroke within 6 months prior to enrollment, uncontrolled angina within 6 months, diagnosed or suspected congenital long QT syndrome, any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), clinically significant abnormality on electrocardiogram (ECG), or pulmonary disease including or greater than grade 2 dyspnea, laryngeal edema, grade 3 pulmonary edema, pulmonary hypertension according to CTCAE 4.03
  • Severe acute or chronic medical or psychiatric condition that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial. This includes but is not limited to the following: Immunosuppressive disease, Chronic renal disease / failure, Concurrent neurodegenerative disease, or Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol.
  • Presence of an acute infection requiring active treatment with antibiotics/antivirals; prophylactic administration is allowed
  • Known history of an autoimmune disorder
  • Known human immunodeficiency virus positivity or acquired immunodeficiency syndrome related illness or other serious medical condition
  • Breastfeeding
  • Received any other therapeutic investigational agent within 30 days of enrollment
  • Contraindication to MRI
  • Foreseeable condition which would preclude the reduction of steroids (dexamethasone) to a maximum of 2 mg BID within the week prior to first administration of study treatment
  • Any concomitant chemotherapy other than standard-dose temozolomide for patients in Cohort A; any concomitant chemotherapy for patients in Cohort B, with the exception of the antiangiogenic humanized monoclonal antibody bevacizumab, which is allowed for patients treated with bevacizumab prior to enrollment in the trial
  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: NCT02010606

Contacts
Contact: Cherry Sanchez, RN 310.423.6839 cherry.sanchez@cshs.org

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Principal Investigator: Jethro Hu, MD         
Sponsors and Collaborators
Cedars-Sinai Medical Center
Investigators
Principal Investigator: Jethro Hu, MD Cedars-Sinai Medical Center
  More Information

No publications provided

Responsible Party: Jethro Hu, Faculty Neuro-Oncologist, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT02010606     History of Changes
Other Study ID Numbers: 33203
Study First Received: December 2, 2013
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Cedars-Sinai Medical Center:
Newly diagnosed glioblastoma
Recurrent glioblastoma
Dendritic cell vaccine
Immunotherapy
Cancer stem cells
Glioma stem cells
Glioma stem-like cells
Cancer stem-like cells
Neurosphere
Therapeutic Uses
Antineoplastic Agents
Neoplasms
Immunologic Factors
Interferon Inducers
Physiological Effects of Drugs
Pharmacologic Actions

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Brain Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Temozolomide
Bevacizumab
Antineoplastic Agents
Interferon Inducers
Physiological Effects of Drugs
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on August 27, 2014