Clinical Trials /

IDH1 Peptide Vaccine for Recurrent Grade II Glioma

NCT02193347

Description:

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:

Phase 1

Trial Eligibility

Document

RESIST: Patients With <span class="go-doc-concept go-doc-biomarker">IDH1</span> Positive Recurrent Grade II <span class="go-doc-concept go-doc-disease">Glioma</span> Enrolled in a Safety and Immunogenicity Study of Tumor-Specific Peptide Vaccine

Title

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

    NCT ID: NCT02193347

    ORG ID: Pro00054746

    Trial Conditions

    Brain Cancer

    Brain Neoplasm, Primary

    Brain Neoplasms, Recurrent

    Brain Tumor

    Cancer of the Brain

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    Potential subjects with recurrent Grade II primary brain tumor that have IDH1 positive
    testing from the first tumor 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 who have not had a tetanus booster within
    10 years will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria
    toxoids adsorbed).

    Within 2 weeks of signing consent eligible subjects will undergo a 1-2 hour leukapheresis
    (to pull off white blood cells) for immune monitoring and within 48 hours vaccine site
    pre-conditioning will be performed 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)
    12-24 hours prior to receiving PEPIDH1M vaccine in the same manner. 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 30 3 days (vaccine #3). All injections will alternate sides. These
    injections will occur without temozolomide (standard of care chemotherapy).

    Seven to 10 days after the 3rd vaccine, subjects will have peripheral blood work drawn for
    immunologic monitoring. This will be followed by surgery to remove the tumor no less than 3
    days and no longer than 7 days after the immunologic monitoring blood work. Tumor samples
    will be evaluated for the IDH1 markers and analyzed for other cells that may have entered
    the tumor.

    Based on 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 21 2 days. Patients that have transitioned to a
    higher Grade brain tumor will not be eligible to continue and will be removed from the
    study. All Adverse Events will be collected from time of consent until off study. For
    purposes of this study, subjects will be considered off study 2 months after the last
    vaccine. Subjects will be followed only for survival thereafter.

    For immune monitoring, a final peripheral blood draw will be performed following 3 months of
    temozolomide and vaccine therapy. Peripheral blood will also be drawn for immune monitoring
    evaluation at progression, if possible.

    For biomarker testing, subjects will have blood and urine collected during the following
    times: prior to vaccine therapy (at consent or leukapheresis visit), prior to vaccine #3,
    prior to surgery to remove the tumor, prior to discharge from hospital following the surgery
    to remove the tumor, prior to each subsequent monthly vaccine administrations, and at
    progression (if possible).

    Subjects will be imaged with contrast-enhanced magnetic resonance imaging (MRI) according to
    standard of care every 2 months 2 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.

    Trial Arms

    Name Type Description Interventions
    PEPIDH1M vaccine Experimental PEPIDH1M vaccine is made up of 500 g of 25 amino acid peptide administered with 150 g of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally.

    Eligibility Criteria

    Inclusion Criteria:

    1. Age 18 years.

    2. IDH1R132H expression in tumor from initial diagnosis

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

    4. Signed informed consent. If the subject's mental status precludes his/her giving
    informed consent, written informed consent may be given by the responsible family
    member or legal representative.

    5. For females of child-bearing potential, negative serum pregnancy test 48 hours prior
    to first treatment with temozolomide (TMZ) or vaccine.

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

    7. Karnofsky Performance Status (KPS) of 60.

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

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

    - Creatinine 1.7 mg/dl.

    10. Adequate hepatic function to tolerate TMZ and surgical resection 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. Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the
    head and neck region (other than TMZ prescribed during radiation for glioma); note
    that prior chemotherapy for a different cancer is allowable.

    4. Severe, active co-morbidity, defined as follows:

    - Unstable angina and/or congestive heart failure requiring hospitalization.

    - Transmural 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.

    - Active connective tissue disorders, such as lupus or scleroderma that in the
    opinion of the treating physician may put the patient at high risk for radiation
    toxicity.

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

    6. Prior allergic reaction to temozolomide.

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

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

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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    The proportion of patients with an unacceptable toxicity will be estimated.

    Secondary Outcome Measures

    IFN ELIspot Measurements

    Trial Keywords

    Immunotherapy

    Adult