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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- James Felker
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Tumor shrinkage or stable disease
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Tumor shrinkage or stable disease
时间窗: 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.
次要结局
未报告次要终点
研究者
James Felker
Assistant Professor
University of Pittsburgh