Glioblastoma Multiforme Multipeptide Vaccine IMA950 and Poly ICLC with or without Varlilumab in Treating Patients with Newly Diagnosed or Recurrent Grade II Glioma

Status: Active

Description

This pilot randomized phase I trial studies the side effects of glioblastoma multiforme multipeptide vaccine IMA950 and poly ICLC and how well they work with or without varlilumab in treating patients with grade II glioma that is newly diagnosed or has come back (recurrent). Vaccines, such as glioblastoma multiforme multipeptide vaccine IMA950, made from peptides may help the body build an effective immune response to kill cancer cells. Immunosuppressive therapy, such as poly ICLC, is used to decrease the body’s immune response. Monoclonal antibodies, such as varlilumab, may interfere with the ability of cancer cells to grow and spread. Giving glioblastoma multiforme multipeptide vaccine IMA950 and poly ICLC with or without varlilumab may work in treating patients with glioma.

Eligibility Criteria

Inclusion Criteria

  • Patients must have a newly diagnosed or recurrent World Health Organization (WHO) grade II astrocytoma, oligoastrocytoma or oligodendroglioma that has been histologically confirmed by prior biopsy or surgical resection; if the pathological diagnosis was made outside of University of California San Francisco (UCSF), the pathology must be reviewed and confirmed at UCSF
  • Patients must be positive for HLA-A2 based on flow­cytometry or genotyping
  • Before enrollment, patients must show non-enhancing T2-fluid-attenuated inversion recovery (FLAIR) lesions that are amenable to surgical resection; surgical resection of at least 0.5 grams of tumor is expected to ensure adequate evaluation of the study endpoints
  • Prior radiation therapy (RT) after initial diagnosis will be allowed but there must be at least 6 months from the completion of RT (or radiosurgery); prior chemotherapy and any systemic molecularly targeted anti-tumor therapy will be allowed, and there must be at least 28 days from the last temodar chemotherapy, 42 days for nitrosourea; at least 14 days from the last dose for chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity
  • Karnofsky performance status (KPS) >= 70%
  • Off or low dose (=< 4 mg/day by Decadron) corticosteroid for at least for 2 weeks before the first pre-surgical vaccine
  • Within 28 days of study registration: Absolute neutrophil (segmented and bands) count (ANC) >= 1.0 x 10^9/L
  • Within 28 days of study registration: Absolute lymphocyte count (ANC) >= 4.0 x 10^8/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) for age
  • Within 28 days of study registration: Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x upper limit of normal (ULN) for age
  • Within 28 days of study registration: 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
  • Women of child­bearing potential 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 (until one month after the last vaccine) since the effects of the current regimen 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
  • Patient must sign an informed consent document indicating that they are aware of the investigational nature of this study, which includes an authorization for the release of their protected health information

Exclusion Criteria

  • Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease
  • Presence of T1 gadolinium (Gd)–enhancing lesions (on magnetic resonance imaging [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 is diagnosed as high-grade glioma (HGG) upon resection after receiving the pre-surgical treatment, 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; will evaluate the tumor tissue to help us develop future approaches for HGG
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with IMA950-poly-ICLC vaccine
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (including active/chronic hepatitis B and C), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • 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., myelodysplatic disorders, marrow failures, acquired immune deficiency syndrome [AIDS], transplant immunosuppression)
  • Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism): antinuclear antibody, thyroid-stimulating hormone (TSH), free thyroxine (FT4), rheumatoid factor
  • Any condition that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
  • Ongoing treatment with immunosuppressive drugs or dexamethasone > 4 mg
  • Use of any of the following concurrent treatment or medications: * Radiation therapy * Chemotherapy * Interferon (e.g. Intron­A) * Allergy desensitization injections * Growth factors (e.g. Procrit, Aranesp, Neulasta) * Interleukins (e.g. Proleukin) * Any investigational therapeutic medication
  • Prior cancer diagnosis except the following: * 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: Nicholas A. Butowski
Email: Nicholas.Butowski@ucsf.edu
UCSF Medical Center-Parnassus
Status: Active
Contact: Nicholas A. Butowski
Phone: 415-353-2966
Email: Nicholas.Butowski@ucsf.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES;

I. 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). (Safety)

II. Determine the response rate and magnitude of CD4+ and CD8+ T-cell responses against the glioblastoma multiforme multipeptide vaccine IMA950 (IMA950) peptides in pre­- and post­-vaccine peripheral blood mononuclear cells (PBMC) using a novel, flow-cytometry-based 2-dimensional (2D) ex vivo assay system. (Immunological activity)

III. Determine whether Arm 1 patients demonstrate higher response rate and/or magnitude of response compared with Arm 2 patients. (Immunological activity)

EXPLORATORY OBJECTIVES:

I. To evaluate whether resected tumors from Arm 1 patients demonstrate significantly higher levels of IMA950-reactive T-cell infiltration and CXCL9/10 expression compared with those resected from Arm 2 (and/or the historical control patients who were enrolled in Institutional Review Board [IRB]# 15-17078 vaccine study).

II. To evaluate whether resected tumors from Arm 1 patients demonstrate significantly higher frequencies of IMA950-reactive T-cell receptor (TCR) clonotypes compared with those resected from Arm 2 (and/or the historical control patients who were enrolled in IRB# 15-17078 vaccine study).

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

IV. To evaluate whether PBMC responses against IMA950 are associated with PFS and frequency of IMA950-reactive T-cells in the tumor.

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

VI. To evaluate phenotype of leukocytes in PBMC samples.

VII. To evaluate the pharmacokinetics (PK) for varlilumab.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive glioblastoma multiforme multipeptide vaccine IMA950 subcutaneously (SC) and poly-ICLC SC on days -23, -16, and -9 and 24-48 hours before standard of care surgery. Patients also receive varlilumab intravenously (IV) over 90 minutes on day -23 and at weeks 1, 7, 13, and 19. Patients then receive glioblastoma multiforme multipeptide vaccine IMA950 SC and poly-ICLC SC at weeks 1, 4, 7, 10, 13, 16, 19, and 22.

ARM II: Patients receive glioblastoma multiforme multipeptide vaccine IMA950 and poly-ICLC as in Arm I.

After completion of study treatment, patients are followed up for 24 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
UCSF Medical Center-Mount Zion

Principal Investigator
Nicholas A. Butowski

Trial IDs

Primary ID 15108
Secondary IDs NCI-2017-01369, 15-18369
Clinicaltrials.gov ID NCT02924038