Poly-ICLC-Assisted Tumor Lysate Vaccines in Treating Patients with Glioma

Status: Active

Description

This phase I trial studies how well poly-ICLC-assisted tumor lysate vaccines work in treating patients with glioma. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill glioma cells.

Eligibility Criteria

Inclusion Criteria

  • Pathological criteria - patients must have a 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 pathologic 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 are amenable to surgical resection 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
  • 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
  • Absolute neutrophil (segmented and bands) count (ANC) >= 1.0 x 10^9/L (within 28 days of study registration)
  • Absolute lymphocyte count (ALC) >= 0.5 x 10^9/L (within 28 days of study registration)
  • Platelets >= 100 x 10^9/L (within 28 days of study registration)
  • Hemoglobin >= 8 g/dL (within 28 days of study registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 28 days of study registration)
  • Serum glutamate pyruvate transaminase (SGPT) alanine aminotransaminase (ALT) =< 2.5 x upper limit of normal (ULN) (within 28 days of study registration)
  • Normal serum creatinine or creatinine clearance >= 60 ml/min/1.73 m^2 (within 28 days of study registration)
  • 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
  • The effects of GBM6-AD-poly vaccine on the developing human fetus are unknown; for this reason and because GBM6-AD-poly vaccine as well as poly-ICIC are unknown to be teratogenic; women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (ex. hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation since the effects of GBM6-AD-poly vaccine on the developing human fetus are unknown; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; WOCBP and male partners of WOCBP should use contraception for 4 weeks after the end of treatment

Exclusion Criteria

  • Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease
  • Presence of T1 gadolinium (Gd) –enhancing lesions (on MRI) suggestive of high-grade glioma
  • Pathological diagnosis for the resected tumor demonstrates transformation to higher grade (i.e. WHO grade III or IV) gliomas; if a patient who received neoadjuvant vaccines is diagnosed as high grade glioma (HGG), the patient will be withdrawn from the study and considered for therapeutic options for HGG (trials for HGG or standard of care); the tumor tissue of such a case would be brought to the lab before the pathological diagnosis is made; and thus would be processed before the lab is informed of the final HGG diagnosis; because HGG tissue may still reflect the vaccine effects, we will evaluate the tumor tissue to help us develop future approaches for HGG
  • Pregnant women are excluded from this study because GBM6-AD-poly vaccine are drugs with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GBM6-AD-poly vaccine breastfeeding should be discontinued if the mother is treated with GBM6-AD-poly vaccine
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • Prior use of bevacizumab
  • History or current status of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) that needed to be treated by systemic therapy, such as immuno-suppressants and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, acquired immune deficiency syndrome [AIDS], transplant immunosuppression)
  • History or clinical suspicion of neurofibromatosis
  • Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism)
  • Any condition that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
  • Ongoing treatment with immunosuppressive drugs
  • Use of any of the following concurrent treatment or medications: * Radiation therapy * Chemotherapy * Interferon (e.g. Intron-A) * Allergy desensitization injections * Growth factors (e.g. Procrit, Aranesp, Neulasta) * Interleukins (e.g. Proleukin) * Any investigational therapeutic medication
  • Prior cancer diagnosis, unless the patient has been disease free for >= 3 years, with the following exceptions: * Squamous cell cancer of the skin without known metastasis * Basal cell cancer of the skin without known metastasis * Carcinoma in situ of the breast (ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS]) * Carcinoma in situ of the cervix
  • Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial
  • Participants with known addiction to any drugs

Locations & Contacts

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: Jennie W. Taylor
Phone: 415-353-2966

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate hypothesis that the neoadjuvant GBM6-AD vaccine admixed with poly-ICLC in patients with resectable World Health Organization (WHO) grade II glioma will be safe and induce increases of T-cell infiltration and up-regulation of CXCL10 in the glioma microenvironment.

II. To evaluate the incidence and severity of adverse events associated with the treatment regime, with an early stopping rule based on the frequency of regimen limiting toxicity (RLT).

III. To evaluate whether surgically resected tumors from Arm 1 (the neoadjuvant arm) patients demonstrate significantly higher levels of tumor-infiltrating CD8+ T-cells and CXCL10 expression compared with those resected from Arm 2 (control) patients.

EXPLORATORY OBJECTIVES:

I. To describe the response rate and magnitude of CD4+ and CD8+ T-cell responses against the GBM6-AD lysate in pre- and post-vaccine peripheral blood mononuclear cells (PBMC) using IFN-gamma-ELISPOT.

II. To describe tumor tissue expression of glioma-associated antigens (GAAs) and antigen-presentation machinery (APM) molecules.

III. To estimate overall survival (OS) and progression-free survival (PFS).

IV. To tabulate tumor objective response rate (ORR) according to low-grade glioma (LGG) Response Assessment in Neuro-Oncology (RANO), if there is measurable tumor after surgery.

V. To evaluate the impacts of the current regimen on systemic tumor-induced immune suppression.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive vaccine glioma lysate vaccine GBM6-AD and poly-ICIC subcutaneously (SC) on days -23, -16, -9, 24-48 hours before surgery, and at weeks 1, 4, 7, 10, 13, 32, and 48 after surgery in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive glioma lysate vaccine GBM6-AD and poly-ICIC SC at weeks 1, 4, 7, 10, 13, 32, and 48 after surgery in the absence of disease progression or unacceptable toxicity.

All patients undergo surgery on day 0.

After completion of study treatment, patients are followed up every 3 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
UCSF Medical Center-Mount Zion

Principal Investigator
Jennie W. Taylor

Trial IDs

Primary ID 15103
Secondary IDs NCI-2017-01683, 15-17692
Clinicaltrials.gov ID NCT02549833