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IDH1 Peptide Vaccine for Recurrent Grade II Glioma (RESIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02193347
Recruitment Status : Active, not recruiting
First Posted : July 17, 2014
Results First Posted : March 15, 2021
Last Update Posted : March 15, 2021
Sponsor:
Information provided by (Responsible Party):
Gary Archer Ph.D., Duke University

Brief 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).

Condition or disease Intervention/treatment 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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
Actual Study Start Date : January 28, 2016
Actual Primary Completion Date : February 3, 2020
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
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 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




Primary Outcome Measures :
  1. Percentage of Participants With an Unacceptable Toxicity [ Time Frame: Date of 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 :
  1. 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 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02193347


Locations
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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Gary Archer Ph.D.
Investigators
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Principal Investigator: Katherine Peters, M.D., Ph.D. Duke University
  Study Documents (Full-Text)

Documents provided by Gary Archer Ph.D., Duke University:
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Responsible Party: Gary Archer Ph.D., Assistant Professor Neurosurgery, Duke University
ClinicalTrials.gov Identifier: NCT02193347    
Other Study ID Numbers: Pro00054746
First Posted: July 17, 2014    Key Record Dates
Results First Posted: March 15, 2021
Last Update Posted: March 15, 2021
Last Verified: February 2021
Keywords provided by Gary Archer Ph.D., Duke University:
Immunotherapy
Adult
Additional relevant MeSH terms:
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Neoplasms
Brain Neoplasms
Recurrence
Disease Attributes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents