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)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Low Grade Glioma
- Sponsor
- James Felker
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Tumor shrinkage or stable disease
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief 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.
Detailed Description
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).
Investigators
James Felker
Assistant Professor
University of Pittsburgh
Eligibility Criteria
Inclusion Criteria
- •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.
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.
Outcomes
Primary Outcomes
Tumor shrinkage or stable disease
Time Frame: Week 24
Participants who demonstrate radiological evidence of tumor shrinkage or stable disease without regimen-limiting toxicity (RLT) after the initial 8 vaccines will be eligible to receive additional vaccinations beginning week 24 and every 6 weeks thereafter for up to two years.