IDH1 Peptide Vaccine for Recurrent Grade II Glioma
Condition: Brain Cancer; Brain Neoplasm, Primary; Brain Neoplasms, Recurrent; Brain Tumor; Cancer of the Brain
MeSH terms: Neoplasms; Brain Neoplasms; Recurrence
Intervention: PEPIDH1M vaccine; Tetanus-Diphtheria Toxoid (Td); Temozolomide
Intervention description: PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.; After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.; Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.
Intervention MeSH terms: Temozolomide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; Adult

Summary:

      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).
    

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
             contraception.

          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
             vaccine.

          9. Unable to undergo MRI imaging.