HLA-A2-Restricted Synthetic Glioma Antigen Peptides Vaccine and Poly-ICLC in Treating Children with Newly Diagnosed High-Grade Glioma, Brainstem Glioma, or Recurrent Unresectable Low-Grade Glioma

Status: Active

Description

This pilot phase I trial studies the side effects and how well HLA-A2-restricted synthetic glioma antigen peptides vaccine and poly ICLC work in treating children with newly diagnosed high-grade glioma, brainstem glioma or low-grade glioma that has come back and can’t be removed by surgery. Vaccines made from small proteins called peptides may help the body build an effective immune response to kill tumor cells that express these glioma-associated peptides. Synthetic ribonucleic acids like poly ICLC may improve the effects of the vaccine. Giving HLA-A2-restricted synthetic glioma antigen peptides vaccine with poly ICLC may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Tumor types – tumor type/location: * Stratum A: newly diagnosed diffuse intrinsic pontine gliomas OR any biopsy proven high-grade glioma involving the brainstem; patients may not have received chemotherapy during or after radiation; patients must be registered within 4-12 weeks of completing radiation * Stratum B: newly diagnosed, non-brainstem high-grade glioma; patients may not have received chemotherapy during or after radiation; patients must be registered within 4-12 weeks of completing radiation * Stratum C: unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens; patients may not have received radiation to the index lesion within 1 year of enrollment * Stratum D: non-brainstem high-grade gliomas that have recurred following treatment * Stratum E: newly diagnosed high-grade gliomas or brain stem gliomas who received chemotherapy during radiation therapy; patients may not have received chemotherapy after radiation therapy was completed; patients must be registered within 4-12 weeks of completing radiation * Stratum F: newly diagnosed high-grade gliomas with metastatic disease within the central nervous system (CNS) requiring craniospinal radiation therapy; patients may or may not have received chemotherapy during radiation, but cannot have received chemotherapy after radiation therapy was completed; patients must be registered within 4-12 weeks of completing radiation
  • HLA-A2 positive based on flow cytometry
  • Patients in Stratum A, B, and E must have received standard involved field radiation therapy (RT) defined as fractionated external beam radiotherapy with total doses between 5000-6000 centigray (cGy); patients in these strata must be registered within 4-12 weeks of completing RT
  • Patients in Stratum F must have received craniospinal radiation
  • Patients must be clinically stable and off or on low-dose (no more than 0.1 mg/kg/day, max 4 mg/day dexamethasone) corticosteroid for at least one week prior to study registration
  • All patients must sign an institutional review board (IRB)-approved informed consent document
  • Patients must have a performance status of >= 70; (Karnofsky if > 16 years and Lansky if < 16 years of age)
  • Documented negative serum beta human chorionic gonadotropin (HCG) for female patients who are post-menarchal; males and females must agree to use effective birth control methods during the course of vaccination (from the first vaccine to two weeks after the last vaccine); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients must be free of systemic infection requiring intravenous (IV) antibiotics at the time of registration; patients must be off IV antibiotics for at least 7 days prior to registration
  • Absolute neutrophil count (ANC) > 1,000/ul
  • Platelets > 100,000/ul (transfusion independent)
  • Absolute lymphocyte count of > 500/uL
  • Hemoglobin > 8 g/dl (may be transfused)
  • Bilirubin =< 1.5x institutional normal for age
  • Serum glutamate pyruvate transaminase (SGPT) alanine transferase (ALT) < 3x institutional normal
  • Serum creatinine based on age or creatinine clearance or radioisotope GFR > 70 ml/min/ml/min/1.73 m^2 * Age 1 to < 2 maximum serum creatinine for male is 0.6; female is 0.6 * Age 2 to < 6 maximum serum creatinine for male is 0.8; female is 0.8 * Age 6 to < 10 maximum serum creatinine for male is 1; female is 1 * Age 10 to < 13 maximum serum creatinine for male is 1.2; female is 1.2 * Age 13 to < 16 maximum serum creatinine for male is 1.5; female is 1.4 * Age >= 16 maximum serum creatinine for male is 1.7; female is 1.4
  • Patients on Strata C and D must have recovered from the toxic effects of prior therapy to grade 1 or better; patients must be at least 3 weeks form the last dose of standard cytotoxic chemotherapy or myelosuppressive biological therapy, at least 1 week from the last dose of non-myelosuppressive biologic therapy and at least 6 months from placement of bis-chloroethylnitrosourea (BCNU) wafers; any questions related to the definition of non-cytotoxic agents should be directed to the principal investigator
  • No overt cardiac, gastrointestinal, pulmonary or psychiatric disease

Exclusion Criteria

  • Presence of metastatic disease for patients in Stratum A, B, D and E; patients with metastatic high grade gliomas diagnosed at < 1 year of age are eligible for Stratum D at the time of recurrence; patients with low grade gliomas (Stratum C) may have tumor spread within the CNS; patients in Stratum F must have tumor spread within the CNS
  • Patients enrolled in Strata A and B may not have received any prior chemotherapy or anti-glioma therapy of any type other than radiation therapy; patients enrolled on Stratum C must have received at least two prior chemotherapy or biologic therapy regimens and may not have received radiation to the index lesion within 1 year of enrollment; patients on Strata A, B, E, and F cannot have received chemotherapy after radiation therapy was completed
  • Concurrent treatment or medications (must be off for at least 1 week) including: * Interferon (e.g. Intron-A) * Allergy desensitization injections * Growth factors (e.g. Procrit, Aranesp, Neulasta) * Interleukins (e.g. Proleukin) * Any investigational therapeutic medication
  • Patients must not have a history of, or currently active autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement
  • Use of immunosuppressives within four weeks prior to study entry or anticipated use of immunosuppressive agents; dexamethasone, or other corticosteroid medications, if used in the peri-operative period and/or during radiotherapy, must be tapered (no more than 0.1 mg/kg/day, max 4 mg/day dexamethasone) for at least one week before study registration; topical corticosteroids are acceptable
  • Patients with known addiction to alcohol or illicit drugs
  • Human immunodeficiency virus (HIV)-positive patients are excluded from the study
  • Patients who have received prior immunotherapy
  • Patients must be registered prior to the start of treatment
  • The date protocol therapy is projected to start must be no later than 7 days after the date of study registration

Locations & Contacts

Pennsylvania

Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: Active
Contact: Gary E. Mason
Phone: 412-692-5056
Email: gary.mason@chp.cdu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Determine the response rate and magnitude of immune response in post-vaccine peripheral blood mononuclear cells (PBMC) against the glioma-associated antigen (GAA) peptides in response to this form of vaccine.

II. Incidence and severity of adverse events associated with the vaccine regimen with an early stopping rule based on the frequency of regimen limiting toxicity (RLT) in each strata.

SECONDARY OBJECTIVES:

I. Radiological response.

II. Overall survival.

III. Tumor tissue for GAA expression status and infiltration of GAA-specific T-cells.

OUTLINE:

Patients receive HLA-A2-restricted synthetic glioma antigen peptides vaccine subcutaneously (SC) and poly-ICLC intramuscularly (IM) on weeks 0, 3, 6, 9, 12, 18, and 21. Beginning at week 27, treatment repeats every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Children's Hospital of Pittsburgh of UPMC

Principal Investigator
Gary E. Mason

Trial IDs

Primary ID Glioma Vaccine
Secondary IDs NCI-2016-00993
Clinicaltrials.gov ID NCT01130077