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

 

Summary

Low-grade gliomas (LGG), which include diffuse astrocytomas, oligodendrogliomas, and oligoastrocytomas, are at extremely high risk to undergo malignant transformation into more aggressive high-grade gliomas (HGG; grades III-IV). Because LGG is considered a premalignant condition for HGG, novel interventions to prevent malignant transformation are being evaluated in patients with LGG.

Vaccine-based immunotherapies may offer a safe and effective option for patients due to the slower growth rate of LGG (in contrast with HGG), which should allow sufficient time for multiple immunizations and therefore high levels of anti-glioma immunity. Because patients with LGGs are generally not as immuno-compromised as patients with HGG, they may also exhibit greater immunological response to and benefit from the vaccines. Further, the generally mild toxicity of vaccines may improve quality of life compared with chemotherapy or radiation therapy.

This clinical trial evaluates the safety and feasibility of a vaccine-based immunotherapy called GBM6-AD in patients with newly diagnosed or recurrent LGG. This vaccine contains glioblastoma lysate, a solution made from ruptured glioblastoma cells, which exposes patients’ immune systems to molecules made by glioma cells. The thought is to train the immune system to recognize unique molecules made by gliomas (also called glioma-specific antigens), so that it learn to recognize and specifically attack glioma cells. In this study, GBM6-AD will be combined with poly ICLC, which is a compound thought to increase tumor-killing activity in various immune cells.

Eligible participants will be randomized into the following treatment groups, which will compare the timing for vaccine administration:

  • Experimental Group: GBM6-AD and poly ICLC (before and after surgery)
  • Active Comparator Group: GBM6-AD and poly ICLC (after surgery only)

 

Inclusion Criteria
  1. 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 UCSF.
  2. 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.
  3. 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)
  4. 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
  5. Patients must be ≥ 18 years old
  6. Patients must have a Karnofsky performance status ≥ 70%
  7. 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
  8. Adequate organ function within 14 days of study registration including:
    1. 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;
    2. Hepatic: - Total bilirubin ≤1.5 x upper limit of normal (ULN) and SGPT (ALT) ≤ 2.5 x upper limit of normal (ULN), and
    3. Renal: Normal serum creatinine or creatinine clearance ≥60 ml/min/1.73 m^2
  9. 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.
  10. 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.

For the most up-to-date description of clinical trial criteria, please visit clinicaltrials.gov

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

For the most up-to-date description of clinical trial criteria, please visit clinicaltrials.gov

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