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

• Sponsor: Precision Life Sciences Group (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01280552
• Collaborator: (none)
• Enrollment: 124
• Locations: 25
• Arms: 2
• Duration (Months): 59
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme	Biological: ICT-107; Biological: Placebo DC	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: Jan 1, 2011
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ICT-107 Autologous dendritic cells pulsed with immunogenic peptides from tumor antigens	Biological: ICT-107; Autologous dendritic cells pulsed with immunogenic antigens
Placebo Comparator: Control Autologous dendritic cells that have not been pulsed with antigens	Biological: Placebo DC; Autologous dendritic cells (DC) that have not been pulsed with antigens

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [2 -3 years]

   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. Overall Survival in HLA-A2 Patients [2-3 years]

   Overall survival in a predefined subpopulation. All randomized patients are included in intent to treat analysis.

Secondary Outcome Measures

1. PFS [2-3 years]

   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. Progression Free Survival in HLA- A2 Patients [2-3 yers]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Female patients of child-bearing potential must have negative serum pregnancy test

2. If not surgically sterile, male and female patients of childbearing age must use double barrier contraception (hormonal; intrauterine device; barrier)

3. Sufficient paraffin embedded tumor sample for analysis MGMT methylation status

4. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birbingham School of Medicine	South Birmingham	Alabama	United States	35294
2	Arizona Cancer Center	Tucson	Arizona	United States	85724
3	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
4	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
5	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
6	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
7	Rush University Medical Center	Chicago	Illinois	United States	60612
8	Jewish Hospital Medical Center	Louisville	Kentucky	United States	40245
9	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21287
10	Massachusetss General Hospital	Boston	Massachusetts	United States	02114
11	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
12	New Jersey Neuroscience Institute	Edison	New Jersey	United States	08818
13	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
14	The Long Island Brain Tumor Center at Neurological Surgery, PC	Great Neck	New York	United States	11021
15	NYU Clinical Cancer Center	New York	New York	United States	10016
16	Weil Cornell Medical College	New York	New York	United States	10065
17	Wake Forest University	Winston Salem	North Carolina	United States	27157
18	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106
19	Cleveland Clinic Rose Ella Burkhardt Brain Tumor and Neuro Oncology Center	Cleveland	Ohio	United States	44195
20	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States	17033
21	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
22	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
23	Sammons Cancer Center (Baylor)	Dallas	Texas	United States	75246
24	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
25	University of Virginia Health System	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• Precision Life Sciences Group

Investigators

• Study Director: Anthony Gringeri, Ph.D., Precision Life Sciences Group

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• ImmunoCellular Therapeutics website

Publications

None provided.

• Responsible Party: Precision Life Sciences Group
• ClinicalTrials.gov Identifier: NCT01280552
• Other Study ID Numbers: ICT-107-201
• First Posted: Jan 20, 2011
• Last Update Posted: Mar 20, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Precision Life Sciences Group: Glioblastoma Multiforme
• Additional relevant MeSH terms: Glioblastoma

Study Results

Participant Flow

Arm/Group Title	ICT-107	Placebo
Arm/Group Description	Autologous dendritic cells pulsed with immunogenic peptides from tumor antigens ICT-107: Autologous dendritic cells pulsed with immunogenic antigens	Autologous dendritic cells that have not been pulsed with antigens Placebo DC: Autologous dendritic cells (DC) that have not been pulsed with antigens
Period Title: Overall Study
STARTED	81	43
COMPLETED	75	42
NOT COMPLETED	6	1

Baseline Characteristics

Arm/Group Title	ICT-107	Placebo	Total
Arm/Group Description	Autologous dendritic cells pulsed with immunogenic peptides from tumor antigens ICT-107: Autologous dendritic cells pulsed with immunogenic antigens	Autologous dendritic cells that have not been pulsed with antigens Placebo DC: Autologous dendritic cells (DC) that have not been pulsed with antigens	Total of all reporting groups
Overall Participants	81	43	124
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	59 72.8%	29 67.4%	88 71%
>=65 years	22 27.2%	14 32.6%	36 29%
Sex: Female, Male (Count of Participants)
Female	37 45.7%	12 27.9%	49 39.5%
Male	44 54.3%	31 72.1%	75 60.5%
Region of Enrollment (participants) [Number]
United States	81 100%	43 100%	124 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	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
Time Frame	2 -3 years

Outcome Measure Data

Analysis Population Description

Intent to treat include all randomized patients

Arm/Group Title	ICT-107	Control Dendritic Cells
Arm/Group Description	Treatment with autologous dendritic cells pulsed with immunogenic peptides	Treatment with autologous dendritic cells not pulsed with immunogenic peptides
Measure Participants	81	43
Median (95% Confidence Interval) [months of survival]	18.3	16.7

2. Secondary Outcome

Title	PFS
Description	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.
Time Frame	2-3 years

Outcome Measure Data

Analysis Population Description

Intent to treat includes all randomized patients

Arm/Group Title	ICT-107	Placebo
Arm/Group Description	Autologous dendritic cells pulsed with immunogenic peptides from tumor antigens ICT-107: Autologous dendritic cells pulsed with immunogenic antigens	Autologous dendritic cells that have not been pulsed with antigens Placebo DC: Autologous dendritic cells (DC) that have not been pulsed with antigens
Measure Participants	81	43
Median (95% Confidence Interval) [months of progression free survival]	11.2	9.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ICT-107, Control Dendritic Cells
	Comments	Stratified log rank p value stratified for age and MGMT methylation status
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	Stratified for age and MGMT methylation status
	Method	Log Rank
	Comments

3. Primary Outcome

Title	Overall Survival in HLA-A2 Patients
Description	Overall survival in a predefined subpopulation. All randomized patients are included in intent to treat analysis.
Time Frame	2-3 years

Outcome Measure Data

Analysis Population Description

Patients with HLA-A2 haplotype

Arm/Group Title	ICT-107	Control
Arm/Group Description	Autologous dendritic cells pulsed with immunogenic peptides from tumor antigens ICT-107: Autologous dendritic cells pulsed with immunogenic antigens	Autologous dendritic cells that have not been pulsed with antigens Placebo DC: Autologous dendritic cells (DC) that have not been pulsed with antigens
Measure Participants	48	29
Median (95% Confidence Interval) [months of survival]	18.3	12.9

4. Secondary Outcome

Title	Progression Free Survival in HLA- A2 Patients
Description	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
Time Frame	2-3 yers

Outcome Measure Data

Analysis Population Description

HLA-A2 patients

Arm/Group Title	ICT-107	Placebo
Arm/Group Description	Autologous dendritic cells pulsed with immunogenic peptides from tumor antigens ICT-107: Autologous dendritic cells pulsed with immunogenic antigens	Autologous dendritic cells that have not been pulsed with antigens Placebo DC: Autologous dendritic cells (DC) that have not been pulsed with antigens
Measure Participants	48	29
Median (95% Confidence Interval) [months of progression free survival]	11.2	7.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ICT-107, Control Dendritic Cells
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments	Analyses were stratified for age and MGMT methylation status.
	Method	Log Rank
	Comments

Adverse Events

Time Frame	3 years
Adverse Event Reporting Description	Safety population was defined as those receiving at least one dose. This included 80 patients for ICT-107 and 43 patients in the Control group.
Arm/Group Title	ICT-107		Placebo
Arm/Group Description	Autologous dendritic cells pulsed with immunogenic peptides from tumor antigens ICT-107: Autologous dendritic cells pulsed with immunogenic antigens		Autologous dendritic cells that have not been pulsed with antigens Placebo DC: Autologous dendritic cells (DC) that have not been pulsed with antigens
All Cause Mortality
	ICT-107		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ICT-107		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/80 (10%)		7/43 (16.3%)
Infections and infestations
infection	4/80 (5%)		4/43 (9.3%)
Nervous system disorders
seizure	8/80 (10%)		7/43 (16.3%)
cerebral edema	2/80 (2.5%)		1/43 (2.3%)
intracranial hemorrhage	4/80 (5%)		0/43 (0%)
increased intracranial pressure	2/80 (2.5%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
pulmonary embolism	0/80 (0%)		3/43 (7%)
Other (Not Including Serious) Adverse Events
	ICT-107		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/80 (73.8%)		40/43 (93%)
Blood and lymphatic system disorders
thrombocytopenia	3/80 (3.8%)		3/43 (7%)
Gastrointestinal disorders
nausea	6/80 (7.5%)		4/43 (9.3%)
General disorders
fatigue	12/80 (15%)		11/43 (25.6%)
Infections and infestations
urinary tract infection	5/80 (6.3%)		2/43 (4.7%)
upper respiratory tract infection	0/80 (0%)		3/43 (7%)
Investigations
white blood cell count decreased	4/80 (5%)		0/43 (0%)
Metabolism and nutrition disorders
decreased appetite	2/80 (2.5%)		3/43 (7%)
Musculoskeletal and connective tissue disorders
musular weakness	2/80 (2.5%)		6/43 (14%)
Nervous system disorders
convulsion	11/80 (13.8%)		7/43 (16.3%)
headache	2/80 (2.5%)		7/43 (16.3%)
hemiparesis	4/80 (5%)		2/43 (4.7%)
partial seizure	5/80 (6.3%)		1/43 (2.3%)
Psychiatric disorders
insomnia	3/80 (3.8%)		4/43 (9.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.