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PEP-CMV in Recurrent MEdulloblastoma/Malignant Glioma (PRiME)

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ClinicalTrials.gov Identifier: NCT03299309
Recruitment Status : Recruiting
First Posted : October 3, 2017
Last Update Posted : June 3, 2019
Sponsor:
Collaborators:
Pediatric Brain Tumor Foundation
Annias Immunotherapeutics, Inc.
Information provided by (Responsible Party):
Gary Archer Ph.D., Duke University

Brief Summary:
The primary goal of this prospective clinical trial is to evaluate the safety of PEP-CMV in patients with recurrent medulloblastoma and malignant glioma. Patients with histologically-proven medulloblastoma or malignant glioma who had received prior therapy for their initial diagnosis and subsequently had tumor recurrence/progression may be enrolled any time after recurrence/progression regardless of prior adjuvant therapy. PEP-CMV is a vaccine comprised of Component A, a synthetic long peptide (SLP) of 26 amino acid residues from human pp65.

Condition or disease Intervention/treatment Phase
Recurrent Medulloblastoma Recurrent Brain Tumor, Childhood Malignant Glioma Drug: PEP-CMV Phase 1

Detailed Description:

Once a patient has enrolled onto this study, prior therapy will be terminated and patients will receive temozolomide 200 mg/m2/day x 5 days. If they are receiving bevacizumab at the time of enrollment, they will continue bevacizumab 10 mg/Kg every 14 days.

Patients who are ≥ 18 years of age will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Tetanus (Td) pre-conditioning vaccine delivered intradermally (i.d.) in the right groin at the site of the vaccine injection 6-24 hours prior to the first vaccine on day 21. The PEP-CMV vaccine will be administered as follows: PEP-CMV Component A mixed with Montanide ISA-51 (1:1 volume ratio) intradermally administered half in the RIGHT groin and half in the LEFT groin.

The first 3 PEP-CMV vaccines will occur every 2 weeks, then PEP-CMV vaccines will continue monthly (+/- 2 weeks) for no more than 10 years. Blood will be obtained for immune system monitoring.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The PRiME Study: PEP-CMV in Recurrent MEdulloblastoma/Malignant Glioma
Actual Study Start Date : June 29, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Experimental: PEP-CMV
Cytomegalovirus (CMV)-specific peptide vaccine (PEP-CMV)
Drug: PEP-CMV
Patients receive temozolomide (TMZ) 200 mg/m2/day x 5 days. On day 20, patients will receive a Tetanus-diphtheria pre-conditioning vaccination with Td (tetanus, diphtheria toxoid, adsorbed). Immunotherapy begins the following day, on day 21, with injection of the PEP-CMV vaccine as follows: PEP-CMV Component A mixed with Montanide ISA-51 intradermally administered half in the RIGHT groin and half in the LEFT groin.
Other Name: PEP-CMV vaccine




Primary Outcome Measures :
  1. Proportion of patients with unacceptable toxicity [ Time Frame: 2 weeks after the 3rd PEP-CMV vaccine on the last enrolled patient ]
    Evaluate the safety of PEP-CMV in pediatric patients with recurrent MB or recurrent Grade III/IV glioma


Secondary Outcome Measures :
  1. Mean or median change from baseline at each follow-up assessment in ELISPOT (IFN-γ) [ Time Frame: 24 months ]
    Quantitate the immune response to the components of the PEP-CMV vaccine by ELISPOT

  2. Mean or median change from baseline at each follow-up assessment in ELISA (gB-KLH) [ Time Frame: 24 months ]
    Quantitate the immune response to the components of the PEP-CMV vaccine by ELISA



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients who are 3 - 35 years old
  2. Histopathologically proven previous diagnosis of medulloblastoma or Grade III or IV glioma.
  3. Radiology evidence of recurrent medulloblastoma (reMB) or recurrent Grade III and IV glioma. Patients will be considered for a biopsy or resection of the recurrent/progressive tumor at the discretion of the treating neurosurgeon and neuro-oncologist.
  4. Brain MRI within one month prior to enrollment.
  5. Received prior therapy for their initial diagnosis prior to recurrence/progression or who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome or NF1 mutation).
  6. Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to registration.
  7. Karnofsky Performance Status (KPS) of ≥ 60% (KPS for > 10 years of age) or Lansky performance Score (LPS) of ≥ 60 (LPS for ≤ 10 years of age) assessed within 2 weeks prior to registration. Patients who are unable to walk because of paralysis but who are up in a wheel chair will be considered ambulatory for the purposes of the performance score.
  8. Bone Marrow:

    • ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported)*.
    • Platelets ≥ 100,000/µl (unsupported)*.
    • Hemoglobin > 8 g/dL (may be supported).
  9. Renal:

    • Serum creatinine ≤ upper limit of institutional normal.

  10. Hepatic:

    • Bilirubin ≤ 1.5 times upper limit of normal for age.
    • SGPT (ALT) ≤ 3 times institutional upper limit of normal for age.
    • SGOT (AST) ≤ 3 times institutional upper limit of normal for age.
  11. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
  12. Signed informed consent according to institutional guidelines must be obtained prior to registration.
  13. Any prior chemoradiotherapy is allowed.

Exclusion Criteria:

  1. Pregnant or need to breast feed during the study period (Negative serum pregnancy test required).
  2. Active infection requiring treatment or an unexplained febrile (> 101.5 degrees F) illness.
  3. Known immunosuppressive disease or human immunodeficiency virus infection.
  4. Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary disease.
  5. Patients receiving concomitant immunosuppressive agents for medical condition.
  6. Patients who need definitive radiotherapy for treatment of recurrent MB or recurrent Grade III or IV glioma.
  7. Patients receiving any other investigational drug therapy.
  8. Patients on corticosteroids > 0.1 mg/Kg/day (i.e. > the maximum dose of 4 mg/day).
  9. Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
  10. Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

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): NCT03299309


Contacts
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Contact: Eric Thompson, MD 919-684-5013 pedsneuronc@duke.edu
Contact: Charlene Flahiff, MS 919-684-5301 pedsneuronc@duke.edu

Locations
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United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Eric Thompson, MD    919-684-5013    pedsneuronc@duke.edu   
Contact: Charlene Flahiff, MS    919-684-5301    pedsneuronc@duke.edu   
Sponsors and Collaborators
Gary Archer Ph.D.
Pediatric Brain Tumor Foundation
Annias Immunotherapeutics, Inc.
Investigators
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Principal Investigator: Eric Thompson, MD Duke University
Principal Investigator: Daniel S Landi, MD Duke University

Additional Information:
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Responsible Party: Gary Archer Ph.D., Assistant Professor of Neurosurgery, Duke University
ClinicalTrials.gov Identifier: NCT03299309     History of Changes
Other Study ID Numbers: Pro00079843
First Posted: October 3, 2017    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gary Archer Ph.D., Duke University:
Glioma
Medulloblastoma
PRiME
Pro00079843
Thompson
Pediatric
Landi

Additional relevant MeSH terms:
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Glioma
Medulloblastoma
Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors, Primitive
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs