A Study of ICT-107 Immunotherapy in Glioblastoma Multiforme (GBM)

Glioblastoma Multiforme Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01280552
• Other study ID #: ICT-107-201
• Status: Completed
• Phase: Phase 2
• First received: January 19, 2011
• Last updated: February 2, 2016
• Start date: January 2011
• Est. completion date: December 2015

Study information

• Verified date: October 2014
• Source: ImmunoCellular Therapeutics, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: December 2015
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Biological:
• ICT-107
Autologous dendritic cells pulsed with immunogenic antigens
• Placebo DC
Autologous dendritic cells (DC) that have not been pulsed with antigens

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Massachusetss General Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Rose Ella Burkhardt Brain Tumor and Neuro Oncology Center	Cleveland	Ohio
United States	Sammons Cancer Center (Baylor)	Dallas	Texas
United States	New Jersey Neuroscience Institute	Edison	New Jersey
United States	The Long Island Brain Tumor Center at Neurological Surgery, PC	Great Neck	New York
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Jewish Hospital Medical Center	Louisville	Kentucky
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	NYU Clinical Cancer Center	New York	New York
United States	Weil Cornell Medical College	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Alabama at Birbingham School of Medicine	South Birmingham	Alabama
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Arizona Cancer Center	Tucson	Arizona
United States	Wake Forest University	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
ImmunoCellular Therapeutics, Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	The objective is to compare overall survival (OS) in patients when treated with ICT 107 versus Control. OS defined as the time from randomization until date of death or the last date patient known alive (if death is not observed) All randomized patients are included in Intent to Treat analysis	2 -3 years	No
Primary	Overall Survival in HLA-A2 Patients	Overall survival in a predefined subpopulation. All randomized patients are included in intent to treat analysis.	2-3 years	No
Secondary	PFS	Secondary Endpoints; PFS is defined as the time from randomization until the date of documented progressive disease (PD) or death, whichever occurs first, or last date known alive and progression free if progression or death is not observed.; Population is all randomized patients ITT.	2-3 years	Yes
Secondary	Progression Free Survival in HLA- A2 Patients	Progression Free Survival in a prespecified subpopulation of patients with HLA-A2 haplotype.; Intent to treat population includes all randomized patients. PFS is defined as the time from randomization until the date of documented progressive disease (PD) or death, whichever occurs first, or last date known alive and progression free if progression or death is not observed	2-3 yers	No

External Links

•   ImmunoCellular Therapeutics website