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

NCT ID: NCT02546102

Last Updated: 2024-04-03

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE3
• Total Enrollment: 234 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-31
• Study Completion Date: 2025-12-31

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.

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

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.

Group Type: EXPERIMENTAL

ICT-107

Intervention Type: BIOLOGICAL

Autologous dendritic cells pulsed with peptides associated with tumor antigens

2

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Control, autologous monocytes-enriched PBMC.

Interventions

ICT-107

Autologous dendritic cells pulsed with peptides associated with tumor antigens

Intervention Type: BIOLOGICAL

Placebo

Control, autologous monocytes-enriched PBMC.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medelis Inc.

INDUSTRY

Sponsor Role: collaborator

Precision Life Sciences Group

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Dignity Health - St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

City of Hope Cancer Center

Duarte, California, United States

UCSD Moores Cancer Center

La Jolla, California, United States

Southern California Permanente Medical Group

Los Angeles, California, United States

University of Southern California

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

University of California Irvine Chao Family Cancer Center

Orange, California, United States

Kaiser Permanente

Redwood City, California, United States

Kaiser Permanente

Sacramento, California, United States

John Wayne Cancer Institute

Santa Monica, California, United States

Stanford Cancer Institute

Stanford, California, United States

University of Colorado Denver

Aurora, Colorado, United States

Associated Neurologists of Southern Connecticut

Fairfield, Connecticut, United States

Smilow Cancer Hospital

New Haven, Connecticut, United States

Christiana Care Health Services

Newark, Delaware, United States

Delray Medical Center

Boca Raton, Florida, United States

Boca Raton Regional Hospital Lynn Cancer Institute

Boca Raton, Florida, United States

Piedmont Hospital

Atlanta, Georgia, United States

Georgia Regents University

Augusta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

NorthShore University Health System

Evanston, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

University of Kentucky

Lexington, Kentucky, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, 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 Michigan Health System

Ann Arbor, Michigan, United States

John Nasseff Neuroscience Institute

Minneapolis, Minnesota, United States

Metro-Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

JFK New Jersey Neuroscience Institute

Edison, New Jersey, United States

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

North Shore University Hospital

Lake Success, New York, United States

Perlmutter Cancer Center

New York, New York, 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

University of Rochester Medical Center

Rochester, New York, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

The Ohio State University Medical Center

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Penn State College of Medicine Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center Cancer Pavilion

Pittsburgh, Pennsylvania, United States

University of Tennessee Medical Cancer Institute

Knoxville, Tennessee, United States

Texas Oncology

Austin, Texas, United States

Baylor Health Charles Sammons Cancer Center

Dallas, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, 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

University of Virginia Health System

Charlottesville, Virginia, 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

Medical University Innsbruck, Dept. of Neurology

Innsbruck, , Austria

Kepler Universitätsklinikum, Neuromed Campus

Linz, , Austria

University Clinic for Neurology

Salzburg, , Austria

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Montreal Neurological Institute & Hospital

Montreal, Quebec, Canada

CHUS Service de Neurochirurgie

Sherbrooke, Quebec, Canada

Countries

United States; Austria; Canada

References

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 glioblastoma. Cancer Immunol Immunother. 2013 Jan;62(1):125-35. doi: 10.1007/s00262-012-1319-0. Epub 2012 Jul 31.

Reference Type: RESULT

PMID: 22847020 (View on PubMed)

Other Identifiers

ICT-107-301

Identifier Type: -

Identifier Source: org_study_id