RecruitingPhase 2NCT02358187

A Vaccine Trial for Low Grade Gliomas

A Phase II Study of Vaccinations With HLA-A2 Restricted Glioma Antigen Peptides in Combination With Poly-ICLC for Children With Recurrent Unresectable Low-Grade Gliomas (LGG)


Sponsor

James Felker

Enrollment

25 participants

Start Date

Jan 1, 2015

Study Type

INTERVENTIONAL

Conditions

Summary

The study will assess the immunogenicity, safety and preliminary clinical efficacy of the glioma associated antigen (GAA)/tetanus toxoid (TT) peptide vaccine and poly-ICLC in HLA-A2+ children with unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens. Radiation therapy counts as one biologic regimen, but patients may not have received radiation to the index lesion within 1 year of enrollment.


Eligibility

Min Age: 12 MonthsMax Age: 21 Years

Inclusion Criteria12

  • Tumor Type
  • Unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens. Radiation therapy counts as a biologic regimen. Patients may not have received radiation therapy to the index lesion within 1 year of enrollment. Patients may have tumor spread within the central nervous system (CNS).
  • HLA-A2 positive based on flow cytometry.
  • 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.
  • Patients must be ≥ 12 months and < 22 years of age at the time of HLA-A2 screening.
  • 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. Because the effect of the peptide-based vaccine and poly-ICLC on the fetus has not sufficiently been investigated, pregnant females will not be included in the study.
  • Patients must be free of systemic infection requiring IV antibiotics at the time of registration. Patients must be off IV antibiotics for at least 7 days prior to registration.
  • Patients with adequate organ function as measured by: Bone marrow: absolute neutrophil count (ANC) > 1,000/µ; Platelets > 100,000/µ (transfusion independent); absolute lymphocyte count of ≥ 500/µ; Hemoglobin >8 g/dl (may be transfused). Hepatic: bilirubin < 1.5x institutional normal for age; serum glutamate pyruvate transaminase (SGPT) < 3x institutional normal.
  • Renal: Serum creatinine based on age or Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 ml/min/ml/min/1.73 m²
  • Patients must have recovered from the toxic effects of prior therapy to grade 1 or better. Patients must be at least 3 weeks from the last dose of standard cytotoxic chemotherapy or myelosuppressive biological therapy and at least 1 week from the last dose of non-myelosuppressive biologic therapy.
  • No overt cardiac, gastrointestinal, pulmonary or psychiatric disease.

Exclusion Criteria12

  • Patients living outside of North America are not eligible.
  • Patients may not have received radiation to the index lesion within 1 year of enrollment.
  • 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 must be tapered to 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.
  • Because patients with immune deficiency are not expected to respond to this therapy, HIV-positive patients are excluded from the study.
  • Patients who have received prior immunotherapy.

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Interventions

BIOLOGICALExperimental: HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC

Poly-ICLC is administered intramuscularly (i.m.) using sterile technique, as supplied from the vial, and in the amount prescribed for the participant's weight. Patients should receive a dose of acetaminophen (15 mg/kg up to a max of 1000 mg) 30-60 minutes before each poly-ICLC administration. The poly-ICLC treatments will be administered immediately following the vaccine. Patients/parents will be asked to report any temperature elevations and side effects after each treatment.


Locations(1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

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NCT02358187


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