Clinical trial NCT01280552: A Study of ICT-107 Immunotherapy in Glioblastoma Multiforme (GBM)
Official title: A Randomized, Double-blind, Controlled Phase IIb Study of the Safety and Efficacy of ICT-107 in Newly Diagnosed Patients With Glioblastoma Multiforme (GBM) Following Resection and Chemoradiation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma Multiforme
Lead sponsor: Precision Life Sciences Group
Sponsor class: INDUSTRY
First posted: 2011-01-20
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 2, multicenter study to determine the safety and efficacy of ICT-107 in treating a type of brain tumor called Glioblastoma Multiforme (GBM). ICT-107 is an immunotherapy in which the patient's immune response will be stimulated to kill the tumor cells. Patients must be newly diagnosed with GBM and not yet received chemoradiation. Some of the patient's white blood cells (WBC) will be removed and cultured in a laboratory with purified antigens, similar to those on GBM cells. The patient's own WBC/DC that have been exposed to the tumor antigens will then be given back to the patient as a vaccine over several months. The goal is for the ICT-107 vaccine to stimulate the patient's immune response to kill the remaining GBM tumor cells after surgery and chemotherapy.

Detailed description: The proposed phase 2 study is a randomized, double blind, controlled study of the safety and efficacy of ICT-107 in newly diagnosed patients with glioblastoma multiforme (GBM) following resection and chemoradiation. The phase 1 clinical trial demonstrated safety and promising efficacy in a small, open-label study. The purpose of this study is to provide information from a larger, controlled clinical trial. Patients must be newly diagnosed with GBM and not yet received chemoradiation. Patients will have had tumor resection, magnetic resonance imaging (MRI) and tumor assessment prior to enrollment into the study. Post surgical treatment consists of 6 weeks of chemotherapy (TMZ) and radiation followed by a washout period. After Screening and informed consent, patients will undergo apheresis at the study site for collection of peripheral blood mononuclear cells (PBMCs). Apheresis product will be sent to a central site where monocytes will be purified and cultured into dendritic cells (DC). DC will be pulsed with synthetic peptides that correspond to immunogenic epitopes of tumor antigens. The pulsed dendritic cells will then be aliquoted and frozen before shipping back to the site. Patients will have the autologous DCs reinfused intradermally. A control group will receive unpulsed autologous DC. Patients will be randomized by age in a 2:1 ratio to ICT-107 or control.Patients will receive at least four intradermal injections of the ICT-107 vaccine and additional vaccine during a maintenance phase. The primary objective is to compare overall survival (OS) and progression free survival (PFS) in patients when treated with ICT-107 versus Control.

Eligibility criteria: Inclusion Criteria:

1. Confirmed, initial diagnosis of GBM. Patients must be newly diagnosed with GBM and not yet received chemoradiation.
2. ≥ 18 years of age
3. HLA-A1 or HLA-A2 positive
4. KPS score of ≥ 70%
5. Baseline hematologic studies and chemistry profiles must meet the following criteria:

   Hemoglobin (Hgb) \> 9.9 g/dL total granulocyte count \> than 1000/mm3 platelet count \> 100,000/mm3 blood urea nitrogen (BUN) \< 30 mg/dL creatinine \< 2 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) ≤ 1.6x control unless therapeutically warranted
6. Female patients of child-bearing potential must have negative serum pregnancy test
7. If not surgically sterile, male and female patients of childbearing age must use double barrier contraception (hormonal; intrauterine device; barrier)
8. Sufficient paraffin embedded tumor sample for analysis MGMT methylation status
9. Written informed consent, Release of Medical Records Form and Health Insurance Portability and Accountability Act (HIPAA) reviewed and signed by patient or legally authorized representatives

Exclusion Criteria:

1. Recurrent disease
2. Radiosurgery including Gamma Knife, linear accelerator based radiosurgery, CyberKnife and placement of Gliadel wafer
3. Presence of any other active malignancy or prior history of malignancy (except for basal cell carcinoma of the skin)
4. Severe pulmonary, cardiac or other systemic disease
5. Congestive heart failure Class III or IV according to New York Heart Association (NYHA)
6. Presence of an acute infection requiring active treatment with antibiotics/antivirals; prophylactic administration is allowed
7. Known history of an autoimmune disorder
8. Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness or other serious medical illness
9. Breastfeeding
10. Received any other therapeutic investigational agent within 30 days of enrollment
11. Reduction of steroids (dexamethasone) to a maximum of 2 mg twice a day (BID) prior to the first administration of study vaccine

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 -3 years
measure: Overall Survival in HLA-A2 Patients
timeFrame: 2-3 years
Secondary outcomes:
measure: PFS
timeFrame: 2-3 years
measure: Progression Free Survival in HLA- A2 Patients
timeFrame: 2-3 yers
Other outcomes:
Locations:
city: South Birmingham
country: United States
facility: University of Alabama at Birbingham School of Medicine
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Louisville
country: United States
facility: Jewish Hospital Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetss General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Edison
country: United States
facility: New Jersey Neuroscience Institute
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Great Neck
country: United States
facility: The Long Island Brain Tumor Center at Neurological Surgery, PC
state: New York
city: New York
country: United States
facility: NYU Clinical Cancer Center
state: New York
city: New York
country: United States
facility: Weil Cornell Medical College
state: New York
city: Winston Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Rose Ella Burkhardt Brain Tumor and Neuro Oncology Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Dallas
country: United States
facility: Sammons Cancer Center (Baylor)
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: Precision Life Sciences Group
name: Anthony Gringeri, Ph.D.
role: STUDY_DIRECTOR
References: