IDH1 Peptide Vaccine for Recurrent Grade II Glioma

NCT02193347 | Completed Phase 1 Results DMC

• 1 other identifier: Pro00054746
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

Immunotherapy; Adult

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an Unacceptable Toxicity

  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.

  Date of consent through 2 months after the last vaccination

Secondary Outcomes (1)

• Percentage of Patients With a Positive Vaccine Response After 3 Post-Surgery Vaccines as Measured by IFNγ ELIspot

  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

Study Arms (1)

PEPIDH1M vaccine

EXPERIMENTAL

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; Biological: Tetanus-Diphtheria Toxoid (Td); Drug: Temozolomide

Interventions

PEPIDH1M vaccine BIOLOGICAL

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.

PEPIDH1M vaccine

Tetanus-Diphtheria Toxoid (Td) BIOLOGICAL

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.

Also known as: Tenivac

PEPIDH1M vaccine

Temozolomide DRUG

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.

Also known as: Temodar

PEPIDH1M vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• IDH1R132H expression in primary tumor
• Radiographic and/or clinical progressive and resectable Grade II glioma.
• Signed informed consent.
• For females of child-bearing potential, negative serum pregnancy test at screening (within 48 hours prior to leukapheresis)
• Women of childbearing potential and male participants must agree to practice adequate contraception.
• Karnofsky Performance Status (KPS) of ≥ 70.
• 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.)
• Adequate renal function as defined below within 2 weeks of enrollment:
• Blood Urea Nitrogen (BUN) ≤ 25 mg/dl.
• Creatinine ≤ 1.7 mg/dl.
• Adequate hepatic function as defined below within 2 weeks of enrollment:

You may not qualify if:

• 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.)
• Metastases detected below the tentorium or beyond the cranial vault.
• 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.
• Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug.
• Prior allergic reaction to temozolomide.
• Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.
• Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine®.
• Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus vaccine.
• Unable to undergo MRI imaging.

Sponsors & Collaborators

• Katy Peters, MD, PhD: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Recurrence

Interventions

Diphtheria-Tetanus Vaccine; Temozolomide

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Katy Peters, M.D., Ph.D.
• Organization: Duke University

katherine.peters@duke.edu

919-684-6173

Study Officials

• Katherine Peters, M.D., Ph.D.

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Neurology and Neurosurgery

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 17, 2014
• Study Start: January 28, 2016
• Primary Completion: February 3, 2020
• Study Completion: February 3, 2020
• Last Updated: December 1, 2023
• Results First Posted: March 15, 2021

Record last verified: 2023-02

Locations

US (1)