Vaccine Therapy and Temozolomide in Treating Patients with Recurrent Glioma Expressing IDH1
- IDH1^R132H expression in primary tumor
- Clinical and/or radiographic, 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 >= 70
- Within 2 weeks of enrollment: Absolute neutrophil count, >= 1500 cells/mm^3
- Within 2 weeks of enrollment: Platelet count, >= 100,000 cells/mm^3
- Within 2 weeks of enrollment: Hemoglobin >= 10 g/dl; (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10 g/dl is acceptable)
- Within 2 weeks of enrollment: Blood urea nitrogen (BUN) =< 25 mg/dl
- Within 2 weeks of enrollment: Creatinine =< 1.7 mg/dl
- Within 2 weeks of enrollment: Bilirubin =< 2.0 mg/dl
- Within 2 weeks of enrollment: Alanine aminotransferase (ALT) =< 3 x normal range
- Within 2 weeks of enrollment: Aspartate aminotransferase (AST) =< 3 x normal range
- 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 Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol * Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
- Pregnant or lactating women
- 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 granulocyte-macrophage colony-stimulating factor (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 magnetic resonance imaging (MRI) imaging
I. To assess the safety of the PEPIDH1M vaccine (IDH1R132H-specific peptide vaccine PEPIDH1M) alone and in combination with adjuvant TMZ (temozolomide) and/or radiation therapy (XRT)/TMZ in adult patients with progressive, resectable World Health Organization (WHO) grade II gliomas that are confirmed grade II or transition to a higher grade glioma at the time of surgery.
I. To assess the immunogenicity of the PEPIDH1M vaccine with adjuvant TMZ using enzyme-linked immunosorbent spot (ELIspot).
I. To describe progression-free survival (PFS) and overall survival (OS).
II. To determine if ELIspot results after vaccination predict PFS or OS.
III. To estimate radiographic response rate prior to surgical resection and PFS after resection using Revised Assessment in Neuro-Oncology (RANO) criteria.
IV. To determine if tumors are IDH1 negative by immunohistochemical analysis and microarray analysis at the time of post-vaccine surgery.
V. To characterize immunologic cell infiltrate in tumors at the time of post-vaccine surgery.
VI. To determine if tumor-specific circulating deoxyribonucleic acid (DNA) containing the c.395G > A (R132H) mutation can be detected in plasma before, during, and after study drug treatment.
VII. To determine if 2-hydroxyglutarate (2-HG), a metabolite specifically produced by tumors with IDH R132H, can be detected in plasma by mass spectrometry before, during, and after study drug treatment.
VIII. To explore the impact of PEPIDH1M vaccination on genetic alternations, differential protein expressions or post-translational modifications (PTMs) using quantitative proteomic strategies in patient-derived samples.
IX. To demonstrate quantitative repeatable measures of metabolism change in IDH1+ gliomas via a standardized magnetic resonance spectroscopy (MRS) protocol, patients will be scanned on the research magnetic resonance (MR) scanner to establish same-day and longitudinal metabolite coefficient of variance and possible longitudinal metabolite changes.
INITIAL VACCINE: Patients receive IDH1R132H-specific peptide vaccine PEPIDH1M in the left and right groin area intradermally (ID) on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity. Patients may receive tetanus toxoid vaccine boost ID one day prior to the first PEPIDH1M peptide vaccine.
SURGERY: Within 7-12 days after the third PEPIDH1M peptide vaccine, patients undergo surgical resection.
VACCINE AND CHEMOTHERAPY: Patients experiencing stable histological grade at recurrence then receive IDH1R132H-specific peptide vaccine PEPIDH1M in the left and right groin area ID on day 22 and temozolomide orally (PO) on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with higher grade gliomas undergoing radiation therapy (RT) receive vaccine #4 prior to RT, vaccine #5 after 4 weeks, and vaccine #6 at the end of RT. Patients then receive vaccines monthly on day 22 for up to 15 doses.
After completion of study treatment, patients are followed up at 1 month and then periodically.
Trial Phase Phase I
Trial Type Treatment
Duke University Medical Center
Katherine Barnett Peters
- Primary ID Pro00054746
- Secondary IDs NCI-2015-02213
- Clinicaltrials.gov ID NCT02193347