The study will assess the immunogenicity, safety and preliminary clinical efficacy of the
GAA/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.
Patients will be treated with subcutaneous injections of GAA/TT-vaccines starting on Week 0
and every 3 weeks thereafter for up to 8 cycles or until Off-treatment criteria are met
(Section 4.6). I.m. poly-ICLC will be administered (30ug/kg i.m.) immediately following the
vaccine. Poly-ICLC should be administered i.m. within 3 cm of the peptide-injection site.
To allow for flexibility with scheduling, the peptide vaccine and Poly-ICLC dose may be given
within one week of the date that the vaccine and poly-ICLC administration are due.
Patients will be evaluated for any possible adverse event, regimen limiting toxicity (RLT) as
well as clinical/radiological responses by clinical visits and MRI scanning. Follow-up MRIs
will be performed (Weeks 6, 15 and 24).
- 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 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
- 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-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
- Patients with adequate organ function as measured by: Bone marrow: 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; SGPT (ALT) < 3x institutional normal.
- Renal: Serum creatinine based on age or Creatinine clearance or radioisotope GFR ≥ 70
- 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.
- Patients living outside of North America are not eligible.
- Patients may not have received radiation to the index lesion within 1 year of
- 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
- 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.
Alberto Broniscer, MD
Children's Hospital of Pittsburgh of UPMC
Alberto Broniscer, MD
Phone: 412 692-5055