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

Phase 3

Suspended

• Conditions: Glioblastoma Multiforme
• Interventions: Biological: Placebo; Biological: ICT-107

• Registration Number: NCT02546102
• Lead Sponsor: Precision Life Sciences Group

Brief 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.

Detailed 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-09-07
• Study First Submitted QC: 2015-09-09
• Study First Posted: 2015-09-10
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-01
• Last Update Posted: 2024-04-03
• Study Start: 2024-12
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 234

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Arm 2 will receive TMZ with a blinded control. Control will be given once a week for 4 weeks in the induction phase. During the maintenance phase, Control will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.
1	ICT-107	Arm 1 will receive ICT-107 in combination with the standard of care, temozolomide (TMZ). ICT-107 will be given once a week for 4 weeks in the induction phase. During the maintenance phase, ICT-107 will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.

Primary Outcome Measures

Name	Time	Method
Overall survival	46 months	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)

Secondary Outcome Measures

Name	Time	Method
Overall survival in patients with methylated MGMT (O6-methylguanine-DNA methyltransferase) tumors	46 months	OS of subjects with methylated MGMT tumors treated with ICT-107 and standard of care vs. control and standard of care.
Type and frequency of treatment emergent adverse events	46 months	Compare the type and frequency of treatment emergent adverse events of ICT-107 vs. control treatment groups
Overall survival in patients with unmethylated MGMT tumors	46 months	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
Progression-free survival	46 months	Progression-free survival (PFS) of subjects treated with ICT-107 and standard of care vs. control and standard of care

Trial Locations

Locations (64)

University of Southern California; 🇺🇸 Los Angeles, California, United States

City of Hope Cancer Center; 🇺🇸 Duarte, California, United States

Piedmont Hospital; 🇺🇸 Atlanta, Georgia, United States

Associated Neurologists of Southern Connecticut; 🇺🇸 Fairfield, Connecticut, United States

New Mexico Cancer Care Alliance; 🇺🇸 Albuquerque, New Mexico, United States

JFK New Jersey Neuroscience Institute; 🇺🇸 Edison, New Jersey, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

University of California Irvine Chao Family Cancer Center; 🇺🇸 Orange, California, United States

Metro-Minnesota Community Oncology Research Consortium; 🇺🇸 Saint Louis Park, Minnesota, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Stanford Cancer Institute; 🇺🇸 Stanford, California, United States

Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Christiana Care Health Services; 🇺🇸 Newark, Delaware, United States

CHUS Service de Neurochirurgie; 🇨🇦 Sherbrooke, Quebec, Canada

University Clinic for Neurology; 🇦🇹 Salzburg, Austria

Perlmutter Cancer Center; 🇺🇸 New York, New York, United States

University of Tennessee Medical Cancer Institute; 🇺🇸 Knoxville, Tennessee, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Juravinski Cancer Centre; 🇨🇦 Hamilton, Ontario, Canada

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Johns Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States

The Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center Cancer Pavilion; 🇺🇸 Pittsburgh, Pennsylvania, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Harvard Medical School Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States

Medical University Innsbruck, Dept. of Neurology; 🇦🇹 Innsbruck, Austria

UCSD Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Southern California Permanente Medical Group; 🇺🇸 Los Angeles, California, United States

John Wayne Cancer Institute; 🇺🇸 Santa Monica, California, United States

Delray Medical Center; 🇺🇸 Boca Raton, Florida, United States

Boca Raton Regional Hospital Lynn Cancer Institute; 🇺🇸 Boca Raton, Florida, United States

Georgia Regents University; 🇺🇸 Augusta, Georgia, United States

NorthShore University Health System; 🇺🇸 Evanston, Illinois, United States

Mount Sinai Medical Center; 🇺🇸 New York, New York, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Weil Cornell Medical Center; 🇺🇸 New York, New York, United States

Penn State College of Medicine Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

Baylor Health Charles Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

Montreal Neurological Institute & Hospital; 🇨🇦 Montreal, Quebec, Canada

John Nasseff Neuroscience Institute; 🇺🇸 Minneapolis, Minnesota, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

University of Texas Health Science Center Memorial Hermann Hospital; 🇺🇸 Houston, Texas, United States

CTRC at UTHSCSA; 🇺🇸 San Antonio, Texas, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, 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

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Dignity Health - St. Joseph's Hospital and Medical Center; 🇺🇸 Phoenix, Arizona, United States

Kaiser Permanente; 🇺🇸 Sacramento, California, United States

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

North Shore University Hospital; 🇺🇸 Lake Success, New York, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

Kepler Universitätsklinikum, Neuromed Campus; 🇦🇹 Linz, Austria

Smilow Cancer Hospital; 🇺🇸 New Haven, Connecticut, United States

Texas Oncology; 🇺🇸 Austin, Texas, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States