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Peptide Targets for Glioblastoma Against Novel Cytomegalovirus Antigens (PERFORMANCE)

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ClinicalTrials.gov Identifier: NCT02864368
Recruitment Status : Recruiting
First Posted : August 12, 2016
Last Update Posted : September 28, 2018
Sponsor:
Collaborators:
Annias Immunotherapeutics, Inc.
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gary Archer Ph.D., Duke University

Brief Summary:
Newly-diagnosed glioblastoma (GBM) with complete or partial surgical resection, CMV seropositive patients will be eligible to enroll on this trial. Following standard of care chemoradiation, eligible subjects will be consented and begin adjuvant temozolomide (TMZ) cycles. Subjects will receive tetanus-diphtheria (Td) pre-conditioning on day 22 of the first post-radiation cycle of TMZ and the following day, receive the first of 3 every other week via intradermal (i.d.) injections of the study drug cytomegalovirus peptide (PEP-CMV), a vaccine mixture comprised in 2 components (referred to as Component A and Component B). The subjects will resume cycles of TMZ, resulting in a ~35-day delay between cycle 1 and 2, and continue PEP-CMV vaccinations every month with cycles of TMZ and then monthly to a maximum of 20 vaccines unless progression occurs.

Condition or disease Intervention/treatment Phase
Glioblastoma Glioblastoma Multiforme Drug: 5-day TMZ Drug: 21-day TMZ Biological: PEP-CMV Drug: Tetanus-Diphtheria booster Drug: Tetanus Pre-Conditioning Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Peptide Targets for Glioblastoma Against Novel Cytomegalovirus Antigens
Actual Study Start Date : December 7, 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tetanus

Arm Intervention/treatment
Experimental: 5-day TMZ
All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine.
Drug: 5-day TMZ
Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle
Other Names:
  • temozolomide
  • Temodar

Biological: PEP-CMV
500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered in the right groin and, 2 hours later, 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered in the left groin

Drug: Tetanus-Diphtheria booster
At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed)
Other Names:
  • Td
  • tetanus

Drug: Tetanus Pre-Conditioning
All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ
Other Names:
  • Td
  • Tetanus-Diphtheria
  • tetanus

Experimental: 21-day TMZ
All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine.
Drug: 21-day TMZ
Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle)
Other Names:
  • temozolomide
  • Temodar

Biological: PEP-CMV
500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered in the right groin and, 2 hours later, 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered in the left groin

Drug: Tetanus-Diphtheria booster
At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed)
Other Names:
  • Td
  • tetanus

Drug: Tetanus Pre-Conditioning
All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ
Other Names:
  • Td
  • Tetanus-Diphtheria
  • tetanus




Primary Outcome Measures :
  1. Incidence of Treatment-related Adverse Events [ Time Frame: 2 weeks after the 3rd vaccine, which is approximately 12 weeks after consent and thereafter, continually through study completion ]
    To assess the safety of PEP-CMV vaccination in combination with adjuvant TMZ, the percentage of patients with unacceptable toxicity will be estimated within each arm. All patients who received any PEP-CMV vaccine will be included in these analyses.

  2. Immunologic Response [ Time Frame: Through study completion, an average of 1.5 years ]
    To determine the TMZ regimen that produces the highest number of T cells that specifically secrete Interferon-gamma (IFNƴ) by ELISPOT in response to component A of PEP-CMV or the highest antibody responses to CMV Glycoprotein B (gB) by ELISA


Secondary Outcome Measures :
  1. Antigen Loss [ Time Frame: Through study completion, an average of 1.5 years ]
    To determine if tumors are CMV antigen negative by immunohistochemical analysis for the presence of the antigen pp65 at the time of disease progression/recurrence



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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. Histopathologically proven newly-diagnosed primary glioblastoma with complete or partial surgical resection. Biopsy not acceptable.
  3. Patients must be CMV seropositive.
  4. The tumor must be supratentorial.
  5. Karnofsky performance status of ≥ 70.
  6. Stable or decreasing steroid dose (≤ 4 mg/day) at time of post-XRT adjuvant TMZ initiation. If patients are decreasing steroid use, once they are at 2 mg/day, they may be supplemented with physiologic replacement hydrocortisone therapy (20-30 mg/day in divided doses), at the discretion of the treating oncologist.
  7. Hematology: ANC ≥ 1500 cells/µL, Platelet count ≥ 100,000 cells/µL, Hemoglobin ≥ 9.0 g/dl
  8. Chemistry: ALT/AST ≤ 2.5 times the upper limit of normal, Total bilirubin ≤ 1.5 mg/dl.

Exclusion Criteria:

  1. Radiographic or cytologic evidence of leptomeningeal or multifocal disease at any time prior to study entry.
  2. Prior conventional antitumor therapy, other than steroids, RT or TMZ therapy given for glioblastoma.
  3. Pregnant or need to breast feed during the study period.
  4. Not adhering to pregnancy prevention recommendations.
  5. Active infection requiring intravenous antibiotics or an unexplained febrile (> 101.5 F) illness.
  6. Immunosuppressive disease or human immunodeficiency virus infection.
  7. Patients with unstable or severe intercurrent medical conditions such as severe heart or lung disease.
  8. Allergic or unable to tolerate TMZ for any reason. Any patient that successfully completed at least 5 weeks of Temodar during standard of care XRT/TMZ and whose blood counts meet the eligibility requirements (inclusion #7) within 4 weeks post XRT/TMZ is eligible.
  9. Known allergy or hypersensitivity to KLH, GM-CSF or yeast derived products, or a history of anaphylactic reactions to shellfish proteins.
  10. Patients with previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies.
  11. Prior allogeneic solid organ transplant.
  12. Currently receiving or ever received immunosuppressive therapy for an autoimmune disorder or an organ transplant.

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): NCT02864368


Contacts
Contact: Denise Jaggers, BSN 919-684-5301 denise.jaggers@duke.edu
Contact: Kristen Fisher 919-684-5301 kristen.fisher@duke.edu

Locations
United States, North Carolina
The Preston Robert Tisch Brain Tumor Center at Duke Recruiting
Durham, North Carolina, United States, 27710
Contact: Kristen Fisher    919-684-5301      
Sponsors and Collaborators
Gary Archer Ph.D.
Annias Immunotherapeutics, Inc.
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
Principal Investigator: David Ashley, MBBS, FRACP, PhD Duke University

Responsible Party: Gary Archer Ph.D., Assistant Professor of Neurosurgery, Duke University
ClinicalTrials.gov Identifier: NCT02864368     History of Changes
Other Study ID Numbers: Pro00034208_1
2R42CA153845-02 ( U.S. NIH Grant/Contract )
First Posted: August 12, 2016    Key Record Dates
Last Update Posted: September 28, 2018
Last Verified: September 2018

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents