Neo-adjuvant Evaluation of Glioma Lysate Vaccines in WHO Grade II Glioma

NCT02549833 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 15-1769215103NCI-2017-01683
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot neoadjuvant vaccine study in adults with WHO grade II glioma, for which surgical resection of the tumor is clinically indicated. Co-primary objectives are to determine: 1) the safety and feasibility of the neoadjuvant approach; and 2) whether the regimen increases the level of type-1 chemokine CXCL10 and vaccine-specific (i.e., reactive to GBM6-AD) CD8+ T-cells in tumor-infiltrating leukocytes (TILs) in the surgically resected glioma.

Conditions

Oligodendroglioma; Astrocytoma, Grade II; Glioma, Astrocytic; Glioma; Malignant Glioma; Oligoastrocytoma, Mixed

Keywords

low-grade glioma; WHO grade II; vaccine; immunotherapy; glioma

Outcome Measures

Primary Outcomes (2)

• Number of Regimen Limiting Toxicity (RLT)

  Delay of the scheduled surgery for longer than 2 weeks due to toxicity of the neoadjuvant treatment will also be considered RLT and reported for each arm will be tabulated with 95% exact (ClopperPearson) confidence intervals

  until disease progression, start of a new therapy, or for a maximum of 18 months from study registration (whichever occurs earlier)

• Measurement of vaccine-induced immune response in the resected tumor

  Evaluate whether surgically resected tumors from Arm 1 (the neoadjuvant arm) patients demonstrate significantly higher levels of CD8+ T-cell infiltration and CXCL10 expression compared with those resected from Arm 2 (control) patients The mean CD8+ T-cells in TILs and CXCL10 expression will be compared between arms by means of a two-sample Student's t test. If the t test assumptions are not met and the data cannot be transformed in such a way that the assumptions are met, a Wilcoxon Rank Sum test will be used

  At time of surgery (as clinically indicated)

Secondary Outcomes (6)

• Response rate of CD4+ and CD8+ T-cell responses against the GM6-AD lysate in pre- and post-vaccine peripheral blood mononuclear cell (PBMC) using IFN-γ-ELISPOT

  at Baseline, At time of surgery (as clinically indicated), Weeks 1, 10 and 16 post-surgery

• Magnitude of response of CD4+ and CD8+ T-cell responses against the GM6-AD lysate in pre- and post-vaccine PBMC using IFN-γ-ELISPOT

  at Baseline, At time of surgery (as clinically indicated), Weeks 1, 10 and 16 post-surgery

• Tumor tissue expression of glioma-associated antigens (GAAs) and antigen-presentation machinery (APM) molecules

  At the time of clinically indicated surgical resection of the tumor

• Overall survival (OS)

  Minimum of 2 years

• Objective response rate (ORR)

  Minimum of 2 years

Study Arms (2)

Vaccines before and after surgery

EXPERIMENTAL

GBM6-AD lysate protein 1 mg and poly-ICLC 1.4 mg administered as one formulation every week leading up to standard-of-care surgery to remove the WHO grade II glioma (Days -23±2, -16±2, -9±2 and 24-48 hours prior to scheduled surgery), every 3 weeks after surgery (Weeks A1, A4, A7, A10, A13, A16; defining Week A1 as the first post-surgery vaccine), and two booster vaccines (Weeks A32 and A48).

Biological: GBM6-AD and poly-ICLC before and after surgery

Vaccines after surgery only

ACTIVE COMPARATOR

GBM6-AD lysate protein 1 mg and poly-ICLC 1.4 mg administered as one formulation every 3 weeks after standard-of-care surgery to remove the WHO grade II glioma only (Weeks A1, A4, A7, A10, A13, A16; defining Week A1 as the first post-surgery vaccine) and two booster vaccines (Weeks A32 and A48). Patients will not receive vaccines before surgery.

Biological: GBM6-AD and poly-ICLC after surgery only

Interventions

GBM6-AD and poly-ICLC before and after surgery BIOLOGICAL

Subcutaneous vaccination with GBM6-AD lysate protein and poly-ICLC combination

Vaccines before and after surgery

GBM6-AD and poly-ICLC after surgery only BIOLOGICAL

Subcutaneous vaccination with GBM6-AD lysate protein and poly-ICLC combination

Vaccines after surgery only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathological criteria - Patients must have newly diagnosed or recurrent WHO grade II glioma (defined as an astrocytoma, oligodendroglioma, or oligoastrocytoma) that is to be histologically confirmed by clinically indicated resection. If patients have already undergone biopsy and have pathological diagnosis of WHO grade II glioma, pathology must be reviewed and confirmed at University of California, San Francisco (UCSF).
• Before enrollment, patients must show supratentorial, non-enhancing T2-FLAIR lesions that need to be surgically resected and are likely WHO grade II glioma. Surgical resection of at least 500 mg tumor tissue to ensure adequate evaluation of the study endpoints.
• Prior radiation therapy (RT) after the initial diagnosis will be allowed. Patients with prior RT must be at least 6 months from the completion of RT (or radiosurgery)
• Prior chemotherapy or molecularly targeted therapy will be allowed. Patients with prior chemotherapy must be at least 6 months from the last dose of chemotherapy or molecularly targeted therapy
• Patients must be ≥ 18 years old
• Patients must have a Karnofsky performance status ≥ 70%
• Patients must be off corticosteroid for at least for 2 weeks before the first neoadjuvant vaccine and for at least 2 weeks prior to the first adjuvant vaccine
• Adequate organ function within 14 days of study registration including:
• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.0 x 10\^9/L; absolute lymphocyte count (ALC) ≥0.5 x 10\^9/L; platelets ≥100 x 10\^9/L; hemoglobin ≥8 g/dL;
• Hepatic: - Total bilirubin ≤1.5 x upper limit of normal (ULN) and serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase (ALT)) ≤ 2.5 x upper limit of normal (ULN), and
• Renal: Normal serum creatinine or creatinine clearance ≥60 ml/min/1.73 m\^2
• Must be free of systemic infection. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment.
• Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device (IUD), surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of the vaccination period. Sexually active males must agree to use barrier contraceptive for the duration of the vaccination period.

You may not qualify if:

• History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, transplant immunosuppression)
• History or clinical suspicion of neurofibromatosis
• Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism)
• Any conditions that could potentially alter immune function (AIDS, multiple sclerosis, uncontrolled diabetes, renal failure)
• Receiving ongoing treatment with immunosuppressive drugs
• Currently receiving any investigational agents or registration on another therapy based trial
• Pregnant or lactating

Sponsors & Collaborators

• Jennie Taylor: lead
• University of Minnesota: collaborator

Study Sites (1)

University of California

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Ogino H, Taylor JW, Nejo T, Gibson D, Watchmaker PB, Okada K, Saijo A, Tedesco MR, Shai A, Wong CM, Rabbitt JE, Olin MR, Moertel CL, Nishioka Y, Salazar AM, Molinaro AM, Phillips JJ, Butowski NA, Clarke JL, Oberheim Bush NA, Hervey-Jumper SL, Theodosopoulos P, Chang SM, Berger MS, Okada H. Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas. J Clin Invest. 2022 Feb 1;132(3):e151239. doi: 10.1172/JCI151239.

  PMID: 34882581 DERIVED

MeSH Terms

Conditions

Oligodendroglioma; Astrocytoma; Glioma; Lymphoma, Follicular

Interventions

Postoperative Period

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Perioperative Period; Surgical Procedures, Operative; Patient Care; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Jennie Taylor, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Hideho Okada, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 20, 2015
• First Posted: September 15, 2015
• Study Start: October 17, 2016
• Primary Completion: August 15, 2022
• Study Completion: August 31, 2024
• Last Updated: November 22, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)