Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma

Glioblastoma Multiforme Clinical Trial

Official title:

A Phase 3 Randomized Double-blind, Controlled Study of ICT-107 With Maintenance Temozolomide (TMZ) in Newly Diagnosed Glioblastoma Following Resection and Concomitant TMZ Chemoradiotherapy

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02546102
• Other study ID #: ICT-107-301
• Status: Suspended
• Phase: Phase 3
• Start date: December 2024
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Precision Life Sciences Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ICT-107 consists of dendritic cells, prepared from autologous mononuclear cells that are pulsed with six synthetic peptides that were derived from tumor associated antigens (TAA) present on glioblastoma tumor cells. This is a Phase 3 study to evaluate ICT-107 in patients with newly diagnosed glioblastoma. Subjects will be randomized to receive standard of care chemoradiation (temozolomide (TMZ) with either ICT-107 or a blinded control. Reinfusion with the pulsed dendritic cells should stimulate cytotoxic T cells to specifically target glioblastoma tumour cells.

Description:

This is a double blind Phase III study where eligible subjects are randomized into two treatment arms following the SOC primary treatment with chemoradiation: Arm 1 will receive ICT-107 in combination with the standard of care, temozolomide (TMZ), Arm 2 will receive TMZ with a blinded control. A 1:1 randomization will be employed, where ARM 1 will receive ICT-107 and Arm 2 will receive placebo control. All subjects must be HLA-A2+. All subjects must have glioblastoma tissue that has tumor assessment for MGMT methylation status prior to randomization (for stratification). Subjects will have had tumor resection and magnetic resonance imaging (MRI) prior to enrollment into the study. After signing of written informed consent and any required privacy compliance forms and screening, enrolled subjects will undergo large volume apheresis at the study site for collection of PBMCs. Apheresis product will be sent to the manufacturing site where both active therapy (ICT-107) and control will be prepared for each subject prior to randomization The study period consists of 4 time periods; a 6-week Post-Surgery Standard of Care Treatment Phase where subjects receive radiotherapy and TMZ; TMZ and radiation to be initiated no more than 8 weeks after surgical resection of glioblastoma; a Rest Period of no more than 14 days where subjects are reassessed for eligibility, and then randomized; a 4 week Induction Phase where study therapy (ICT-107 or Control) is given weekly; followed by a Maintenance Phase where study therapy is given monthly for 11 months, and then every 6 months until either progression, withdrawal from the study, death, or the supply of autologous study therapy is exhausted. Randomized subjects will receive 4 weekly administrations of subject-specific study therapy (ICT-107 or Control) during the Induction Phase. No TMZ will be given during the 4 week Induction Phase. Each study therapy injection will be delivered intradermally (axilla).

The Maintenance Phase will consist of administration of subject-specific study therapy monthly for 11 months after the Induction Phase (for a total of 15 injections over 12 months during the Induction and Maintenance Phases), and then every 6 mos. thereafter until depletion or confirmation of progressive disease (PD). During the Maintenance Phase (where ICT-107 or control are given monthly), the administration of TMZ and subject specific study therapy or control will be separated in time by approximately 2 weeks (see Section 9.1.4). Pre-treatment, treatment and assessment schedules will be the same for all subjects.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 234
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects must understand and sign the study specific informed consent

2. Subjects must be in primary remission

3. Subjects should have < 1 cm3 disease by MRI within the previous 4 weeks (by central read)

4. Subjects must be HLA-A2 positive by central lab

5. Subjects must have adequate renal, hepatic and bone marrow function based on screening laboratory assessments. Baseline hematologic studies and chemistry and coagulation profiles must meet the following criteria:

1. Hemoglobin (Hgb) > 8 g/dL

2. Absolute Neutrophil Count (ANC) > 1000/mm3

3. Platelet count > 100,000/mm3

4. Blood Urea Nitrogen (BUN) < 30 mg/dL

5. Creatinine < 2 mg/dL

6. Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2 x upper limit of normal (ULN)

7. Prothrombin Time (PT) and activated partial thromboplastin time (PTT) = 1.6x unless therapeutically warranted

6. Subjects must use effective contraceptive methods during the study and for three months following the last dose of study product, if of reproductive age and still retain fertility potential.

7. Subjects must have at least one positive DTH skin response (more than 5 mm) to test item challenge prior to randomization.

Exclusion Criteria:

1. Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used for prevention of severe neutropenia).

2. Subjects with glioblastoma mutated IDH by Immunohistochemistry (IHC)

3. Subjects with concurrent conditions that would jeopardize the safety of the subject or compliance with the protocol.

4. Subjects with a history of chronic or acute hepatitis C or B infection.

5. Subjects require or are likely to require more than a 2-week course of corticosteroids for intercurrent illness. Subjects must have completed the course of corticosteroids at the time of apheresis to meet eligibility.

6. Subjects have any acute infection that requires specific therapy. Acute therapy must have been completed within seven days prior to study enrollment.

7. Subjects with active other malignancy diagnosed in the past 3 years (excepting in situ tumors)

8. Subjects known to be pregnant or nursing.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Biological:
• ICT-107
Autologous dendritic cells pulsed with peptides associated with tumor antigens
• Placebo
Control, autologous monocytes-enriched PBMC.

Locations

Country	Name	City	State
Austria	Medical University Innsbruck, Dept. of Neurology	Innsbruck
Austria	Kepler Universitätsklinikum, Neuromed Campus	Linz
Austria	University Clinic for Neurology	Salzburg
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Montreal Neurological Institute & Hospital	Montreal	Quebec
Canada	CHUS Service de Neurochirurgie	Sherbrooke	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Piedmont Hospital	Atlanta	Georgia
United States	Georgia Regents University	Augusta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Texas Oncology	Austin	Texas
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boca Raton Regional Hospital Lynn Cancer Institute	Boca Raton	Florida
United States	Delray Medical Center	Boca Raton	Florida
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Harvard Medical School Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Baylor Health Charles Sammons Cancer Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	City of Hope Cancer Center	Duarte	California
United States	JFK New Jersey Neuroscience Institute	Edison	New Jersey
United States	NorthShore University Health System	Evanston	Illinois
United States	Associated Neurologists of Southern Connecticut	Fairfield	Connecticut
United States	Penn State College of Medicine Hershey Medical Center	Hershey	Pennsylvania
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Texas Health Science Center Memorial Hermann Hospital	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Tennessee Medical Cancer Institute	Knoxville	Tennessee
United States	UCSD Moores Cancer Center	La Jolla	California
United States	North Shore University Hospital	Lake Success	New York
United States	University of Kentucky	Lexington	Kentucky
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Southern California Permanente Medical Group	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	John Nasseff Neuroscience Institute	Minneapolis	Minnesota
United States	Smilow Cancer Hospital	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Perlmutter Cancer Center	New York	New York
United States	Weil Cornell Medical Center	New York	New York
United States	Christiana Care Health Services	Newark	Delaware
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of California Irvine Chao Family Cancer Center	Orange	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Dignity Health - St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	University of Pittsburgh Medical Center Cancer Pavilion	Pittsburgh	Pennsylvania
United States	Kaiser Permanente	Redwood City	California
United States	University of Rochester Medical Center	Rochester	New York
United States	Kaiser Permanente	Sacramento	California
United States	Metro-Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	CTRC at UTHSCSA	San Antonio	Texas
United States	John Wayne Cancer Institute	Santa Monica	California
United States	Ivy Center for Advanced Brain Tumor Treatment Swedish Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Stanford Cancer Institute	Stanford	California
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Precision Life Sciences Group	Medelis Inc.

Countries where clinical trial is conducted

United States,  Austria,  Canada, 

References & Publications (1)

Phuphanich S, Wheeler CJ, Rudnick JD, Mazer M, Wang H, Nuno MA, Richardson JE, Fan X, Ji J, Chu RM, Bender JG, Hawkins ES, Patil CG, Black KL, Yu JS. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblas — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival (OS) of subjects treated with ICT-107 and standard of care (radiation (RT) and TMZ) vs. placebo control and standard of care (RT and TMZ)	46 months
Secondary	Overall survival in patients with unmethylated MGMT tumors	OS of subjects with unmethylated MGMT (O6-methylguanine-DNA methyltransferase) tumors treated with ICT-107 and standard of care vs. control and standard of care	46 months
Secondary	Overall survival in patients with methylated MGMT (O6-methylguanine-DNA methyltransferase) tumors	OS of subjects with methylated MGMT tumors treated with ICT-107 and standard of care vs. control and standard of care.	46 months
Secondary	Progression-free survival	Progression-free survival (PFS) of subjects treated with ICT-107 and standard of care vs. control and standard of care	46 months
Secondary	Type and frequency of treatment emergent adverse events	Compare the type and frequency of treatment emergent adverse events of ICT-107 vs. control treatment groups	46 months