Vaccine treatment for children with 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)

This study is testing a new vaccine treatment for children with hard-to-treat low-grade brain tumors to see if it can help their condition after they’ve already tried other treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 12 Months to 21 Years
• Sex: All
• Sponsor: University of Pittsburgh (other)
• Drugs / interventions: chemotherapy, immunotherapy, Radiation
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT02358187 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, immunogenicity, and preliminary efficacy of a glioma-associated antigen peptide vaccine combined with poly-ICLC in children with unresectable low-grade gliomas who have undergone at least two prior chemotherapy or biologic treatments. Participants will receive subcutaneous injections of the vaccine every three weeks for up to eight cycles, alongside intramuscular administration of poly-ICLC. The study will monitor patients for adverse events and clinical responses through regular MRI scans and clinical visits.

Who should consider this trial

Good fit: Ideal candidates are HLA-A2 positive children aged 12 months to 22 years with unresectable low-grade gliomas who have received at least two prior treatments.

Not a fit: Patients who have undergone radiation therapy to the index lesion within the past year or those with resectable tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new immunotherapy option for children with difficult-to-treat low-grade gliomas.

How similar studies have performed: While similar immunotherapy approaches have shown promise in other cancers, this specific combination is novel and has not been extensively tested in low-grade gliomas.

Eligibility criteria

Inclusion Criteria:

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 Criteria:

* 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.

Where this trial is running

Pittsburgh, Pennsylvania

• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: James Felker, MD — University of Pittsburgh
• Study coordinator: James Felker, MD

Conditions: Low Grade Glioma