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

• ClinicalTrials.gov Identifier: NCT03299309
• Recruitment Status: Active, not recruiting
• First Posted: October 3, 2017
• Last Update Posted: May 18, 2023
• Sponsor: Daniel Landi
• Collaborators: Pediatric Brain Tumor Foundation; Annias Immunotherapeutics, Inc.
• Information provided by (Responsible Party): Daniel Landi, Duke University

Study Description

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. In May 2021, enrollment on the study was temporarily suspended due to delays in vialing the PEP-CMV study vaccine.

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.

In May 2021, enrollment on the study was temporarily suspended due to delays in vialing the PEP-CMV study vaccine.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• 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
• Actual Primary Completion Date: April 27, 2023
• Estimated Study Completion Date: April 2025

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

Locations

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Daniel Landi

Pediatric Brain Tumor Foundation

Annias Immunotherapeutics, Inc.

Investigators

• Principal Investigator: Daniel Landi, MD; Duke University

More Information

Additional Information:

The Preston Robert Tisch Brain Tumor Center at Duke 

Duke Cancer Institute 

• Responsible Party: Daniel Landi, Assistant Professor of Pediatrics and Neurosurgery, Duke University
• ClinicalTrials.gov Identifier: NCT03299309
• Other Study ID Numbers: Pro00079843
• First Posted: October 3, 2017
• Last Update Posted: May 18, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Daniel Landi, Duke University:

Glioma; Medulloblastoma; PRiME; Pro00079843; Thompson; Pediatric; Landi

Additional relevant MeSH terms:

Glioma; Brain Neoplasms; Medulloblastoma; Recurrence; Disease Attributes; Pathologic Processes; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroectodermal Tumors, Primitive; Vaccines; Immunologic Factors; Physiological Effects of Drugs