Patients With IDH1 Positive Recurrent Grade II Glioma Enrolled in a Safety and Immunogenicity Study of Tumor-Specific Peptide Vaccine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Percentage of Participants With an Unacceptable Toxicity
研究概览
简要总结
Potential subjects with progressive Grade II primary brain tumor that have IDH1 positive testing from the primary tumor (initial diagnosis) will be offered this treatment study in order to test the safety of the PEPIDH1M vaccine in combination with standard chemotherapy (temozolomide).
详细描述
After informed consent has been signed, subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen.
Eligible subjects will undergo a 1-2 hour leukapheresis (to pull off white blood cells) for immune monitoring. Within 48 hours of leukapheresis, subjects will receive vaccine site pre-conditioning as a single dose of Td toxoid (in a total volume of 0.4 mLs salt water/saline) given in the intradermal space (just under the surface of the skin) to the right groin area. The pre-conditioning will be administered one day prior to receiving PEPIDH1M vaccine. The peptide vaccine is administered in the upper thigh area approximately 4 inches below the groin in the intradermal space as vaccine # 1. Subsequent vaccines will be given on day 15 ±3 days (vaccine #2) and day 29 ±3 days (vaccine #3). Each injection of the peptide vaccine will be given half on the right groin and half on the left groin. The first 3 peptide vaccine injections will occur without temozolomide (standard of care chemotherapy).
Seven to twelve days after the 3rd vaccine, subjects will have standard of care surgery to remove the tumor. Tumor samples will be evaluated for the IDH1 markers and analyzed for other cells that may have entered the tumor.
Based on the the tissue obtained at surgery, subjects with stable histologic grade at recurrence will then be treated with vaccine and temozolomide. During monthly cycles of temozolomide, subjects will receive the vaccine on day 22 (+ 2 days) for a maximum of 15 total vaccines (which includes the first 3 bi-weekly vaccines). Patients that have transitioned to a higher grade brain tumor at the time of surgery will receive temozolomide and radiation therapy per standard of care and monthly vaccines (vaccines #4-6). After completion of radiation therapy, subjects in this treatment group will receive vaccines monthly on day 22 (+2 days) with post-RT cycles of TMZ to a maximum of 15 vaccines.
All Adverse Events will be collected from time of consent until off study. The treatment phase of the study will end 1 month after the last vaccine. Patients will be followed only for overall survival, progression-free survival, and subsequent therapies thereafter.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •IDH1R132H expression in primary tumor
- •Radiographic and/or clinical progressive and resectable Grade II glioma.
- •Signed informed consent.
- •For females of child-bearing potential, negative serum pregnancy test at screening (within 48 hours prior to leukapheresis)
- •Women of childbearing potential and male participants must agree to practice adequate contraception.
- •Karnofsky Performance Status (KPS) of ≥
- •Complete Blood Count (CBC)/differential with adequate bone marrow function as defined below within 2 weeks of enrollment:
- •Absolute neutrophil count, ≥ 1500 cells/mm
- •Platelet count, ≥ 100,000 cells/mm
- •Hemoglobin ≥ 10 g/dl. (Note: the use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
- •Adequate renal function as defined below within 2 weeks of enrollment:
- •Blood Urea Nitrogen (BUN) ≤ 25 mg/dl.
- •Creatinine ≤ 1.7 mg/dl.
- •Adequate hepatic function as defined below within 2 weeks of enrollment:
- •Bilirubin ≤ 2.0 mg/dl.
- •Alanine Aminotransferase (ALT) ≤ 3 x normal range.
- •Aspartate Aminotransferase (AST) ≤ 3 x normal range
排除标准
- •Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible.)
- •Metastases detected below the tentorium or beyond the cranial vault.
- •Severe, active co-morbidity, defined as follows:
- •Unstable angina and/or congestive heart failure requiring hospitalization.
- •Myocardial infarction within the last 6 months.
- •Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because treatments involved in this protocol may be significantly immunosuppressive.
- •Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
- •Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug.
- •Prior allergic reaction to temozolomide.
- •Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.
- •Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine®.
- •Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus vaccine.
- •Unable to undergo MRI imaging.
研究组 & 干预措施
PEPIDH1M vaccine
PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.
干预措施: PEPIDH1M vaccine (Biological)
PEPIDH1M vaccine
PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.
干预措施: Tetanus-Diphtheria Toxoid (Td) (Biological)
PEPIDH1M vaccine
PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Percentage of Participants With an Unacceptable Toxicity
时间窗: Date of consent through 2 months after the last vaccination
The percentage of patients who experience an unacceptable toxicity defined as any Grade 3 toxicity at least possibly attributed to the vaccine (or vaccine + TMZ and/or RT) that does not resolve to baseline within 3 weeks, any Grade 3 hypersensitivity reactions requiring steroids, any Grade 4 toxicity, including neurologic events not due to progressive disease, or any life threatening-event not attributable to concomitant medication, co-morbid event, or disease progression.
次要结局
- Percentage of Patients With a Positive Vaccine Response After 3 Post-Surgery Vaccines as Measured by IFNγ ELIspot(From time of pheresis #1, one day prior to first pre-surgery vaccine dose, until the time of the third post-surgery vaccination, an expected average of 24 weeks after study initiation)
研究者
Katy Peters, MD, PhD
Associate Professor, Neurology and Neurosurgery
Duke University