Clinical Trials /

IDH1 Peptide Vaccine for Recurrent Grade II Glioma



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).

Related Conditions:
  • Glioma
Recruiting Status:

Active, not recruiting


Phase 1

Trial Eligibility



  • Brief Title: IDH1 Peptide Vaccine for Recurrent Grade II Glioma
  • Official Title: Patients With IDH1 Positive Recurrent Grade II Glioma Enrolled in a Safety and Immunogenicity Study of Tumor-Specific Peptide Vaccine

Clinical Trial IDs

  • ORG STUDY ID: Pro00054746
  • NCT ID: NCT02193347


  • Brain Cancer
  • Brain Neoplasm, Primary
  • Brain Neoplasms, Recurrent
  • Brain Tumor
  • Cancer of the Brain


PEPIDH1M vaccinePEPIDH1M vaccine
Tetanus-Diphtheria Toxoid (Td)TenivacPEPIDH1M vaccine
TemozolomideTemodarPEPIDH1M vaccine


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).

Detailed Description

      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.

      Subjects will have blood collected for immune monitoring and biomarker testing during the
      following times: prior to initiating vaccine therapy (at the leukapheresis visit), prior to
      surgery to remove the tumor, at the clinic visit prior to starting first cycle of
      temozolomide after surgery (or radiation therapy and temozolomide for those who transition to
      higher grade), at vaccine #6, and at end of vaccine treatment (1 month after vaccine #15 or
      time the subject comes off study, whichever comes first).

      Subjects will be imaged with contrast-enhanced magnetic resonance imaging (MRI) according to
      standard of care every 10 weeks (+/- 4 weeks) while on temozolomide and afterward, per the
      treating neuro-oncologist's recommendation. Revised Assessment in Neuro-Oncology (RANO)
      criteria will be used for assessment of pseudoprogression and tumor progression. Subjects
      demonstrating definitive progression will be removed from study.

      As part of standard care for these subjects, upon tumor progression, participants may undergo
      biopsy or resection. As this is not a research procedure, consent will be obtained
      separately. Subjects that have this procedure done within the Duke University Health System
      will be asked to have a portion of the tumor sample, if possible, to assess immunologic cell
      infiltration, antigen expression, and biomarkers for immunologic response.

      Please note, data collection will continue to occur outside of the defined primary and
      secondary outcomes for exploratory objectives.

      The specific exploratory objective involves describing the progression free survival (PFS)
      and overall survival (OS). The endpoint is the proportion of patients alive without disease
      progression 6 months after initial vaccine treatment, and both the median PFS, and the median

      The objective will be reviewed at 3 years after the last subject came off study.

Trial Arms

PEPIDH1M vaccineExperimentalPEPIDH1M 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.
  • PEPIDH1M vaccine
  • Tetanus-Diphtheria Toxoid (Td)
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years.

          2. IDH1R132H expression in primary tumor

          3. Radiographic and/or clinical progressive and resectable Grade II glioma.

          4. Signed informed consent.

          5. For females of child-bearing potential, negative serum pregnancy test at screening
             (within 48 hours prior to leukapheresis)

          6. Women of childbearing potential and male participants must agree to practice adequate

          7. Karnofsky Performance Status (KPS) of ≥ 70.

          8. Complete Blood Count (CBC)/differential with adequate bone marrow function as defined
             below within 2 weeks of enrollment:

               -  Absolute neutrophil count, ≥ 1500 cells/mm3.

               -  Platelet count, ≥ 100,000 cells/mm3.

               -  Hemoglobin ≥ 10 g/dl. (Note: the use of transfusion or other intervention to
                  achieve Hgb ≥ 10 g/dl is acceptable.)

          9. Adequate renal function as defined below within 2 weeks of enrollment:

               -  Blood Urea Nitrogen (BUN) ≤ 25 mg/dl.

               -  Creatinine ≤ 1.7 mg/dl.

         10. 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

        Exclusion Criteria:

          1. 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.)

          2. Metastases detected below the tentorium or beyond the cranial vault.

          3. 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.

          4. Pregnant or lactating women, due to possible adverse effects on the developing fetus
             or infant due to study drug.

          5. Prior allergic reaction to temozolomide.

          6. Patients treated on any other therapeutic clinical protocols within 30 days prior to
             study entry or during participation in the study.

          7. Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any
             component of Leukine®.

          8. Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus

          9. Unable to undergo MRI imaging.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With an Unacceptable Toxicity
Time Frame:Date of consent through 2 months after the last vaccination
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Percentage of Evaluable Subjects Who Had a Response Greater Than 20 Spot-forming Cells (SFC) Per 10^6 Lymphocytes
Time Frame: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
Safety Issue:
Description:The number of spot-forming cells (SFC) per 10^6 lymphocytes measured by ELISpot. A blue-black colored precipitate forms and appears as spots at the sites of cytokine localization, with each individual spot representing an individual analyte-secreting cell.


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Gary Archer Ph.D.

Trial Keywords

  • Immunotherapy
  • Adult

Last Updated

March 15, 2021