A Vaccine Trial for Low Grade Gliomas

Официальное название

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)

Обзор

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.

Подробное описание

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).

Вмешательства

• Биопрепарат Experimental: 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.

Первичные конечные точки

• Tumor shrinkage or stable disease [Срок оценки: Week 24]

Критерии участия

Критерии включения

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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Children's Hospital of Pittsburgh of UPMC — Pittsburgh

Идентификаторы

NCT: NCT02358187 · STUDY19060121 · R01CA187219 · PRO13110086

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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