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IDH1 Peptide Vaccine for Recurrent Grade II Glioma (RESIST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Duke University
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT02193347
First received: July 2, 2014
Last updated: April 10, 2017
Last verified: April 2017
  Purpose
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).

Condition Intervention Phase
Brain Cancer
Brain Neoplasm, Primary
Brain Neoplasms, Recurrent
Brain Tumor
Cancer of the Brain
Biological: PEPIDH1M vaccine
Biological: Tetanus-Diphtheria Toxoid (Td)
Drug: Temozolomide
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Patients With IDH1 Positive Recurrent Grade II Glioma Enrolled in a Safety and Immunogenicity Study of Tumor-Specific Peptide Vaccine

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • The percentage of patients with an unacceptable toxicity will be estimated. [ Time Frame: Adverse events will be recorded from the time the subject signs the 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.


Secondary Outcome Measures:
  • IFNγ ELIspot Measurements [ Time Frame: Levels of immune response will be examined after 3 vaccinations (i.e., pre-surgery) as well as after 3 additional post-surgery vaccinations, an expected average of 24 weeks after study initiation. ]
    The mean difference in the number of spot-forming cells (SFC) per 10^6 lymphocytes cultured with and without IDH1 peptide will be calculated. A response will be considered positive if this value is greater than 20 SFC per 10^6 lymphocytes after determining the level of detection in the IDH ELISpot.


Estimated Enrollment: 24
Study Start Date: December 2015
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: PEPIDH1M vaccine
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.
Biological: Tetanus-Diphtheria Toxoid (Td)
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 twelve hours to one day prior to receiving the first PEPIDH1M vaccine.
Other Name: Tenivac
Drug: Temozolomide
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.
Other Name: Temodar

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 twelve hours to 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. 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.

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 progression (if possible).

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02193347

Contacts
Contact: Susan Boulton, RN, BSN 919-668-0896 susan.boulton@dm.duke.edu
Contact: Sarah Woodring, CRC 919-684-2527 sarah.woodring@duke.edu

Locations
United States, North Carolina
Duke Comprehensive Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Clinical Trials Office - Duke Comprehensive Cancer Center    888-275-3853      
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Katherine Peters, M.D., Ph.D. Duke University
  More Information

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02193347     History of Changes
Other Study ID Numbers: Pro00054746
Study First Received: July 2, 2014
Last Updated: April 10, 2017

Keywords provided by Duke University:
Immunotherapy
Adult

Additional relevant MeSH terms:
Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vaccines
Temozolomide
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 26, 2017