PEP-CMV in Treating Participants with Recurrent Medulloblastoma or Malignant Glioma
This phase I trial studies how well the peptide (PEP)-cytomegalovirus (CMV) vaccine works in treating participants with medulloblastoma or malignant glioma that has come back (recurrent). Vaccine made from peptides derived from CMV antigens may help the body build an effective immune response to kill tumor cells.
Inclusion Criteria
- Histopathologically proven previous diagnosis of medulloblastoma or grade III or IV glioma
- Radiology evidence of 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
- Brain MRI within one month prior to enrollment
- Received prior therapy for their initial diagnosis 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)
- Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to initiating temozolomide study drug
- 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
- ANC (Absolute neutrophil count) >= 1000/ul (unsupported)
- Platelets >= 100,000/ul (unsupported)
- Hemoglobin > 8 g/dL (may be supported)
- Serum creatinine =< upper limit of institutional normal
- Bilirubin =< 1.5 times upper limit of normal for age
- Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 3 times institutional upper limit of normal for age
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 3 times institutional upper limit of normal for age
- 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
- Signed informed consent according to institutional guidelines must be obtained prior to registration
- Any prior chemoradiotherapy is allowed
Exclusion Criteria
- Pregnant or need to breast feed during the study period (negative serum pregnancy test required)
- Active infection requiring treatment or an unexplained febrile (> 101.5 degrees Fahrenheit [F]) illness
- Known immunosuppressive disease or human immunodeficiency virus infection
- Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary disease
- Patients receiving concomitant immunosuppressive agents for medical condition
- Patients who need definitive radiotherapy for treatment of recurrent MB or recurrent grade III or IV glioma
- Patients receiving any other investigational drug therapy
- Patients on corticosteroids > 0.1 mg/Kg/day (i.e. > the maximum dose of 4 mg/day)
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction
- Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03299309.
PRIMARY OBJECTIVE:
I. To evaluate the safety of PEP-CMV in pediatric patients with recurrent medulloblastoma (reMB) or recurrent grade III/IV glioma.
SECONDARY OBJECTIVE:
I. To quantitate the immune response to the components of the PEP-CMV vaccine by enzyme-linked immunospot assay (ELISPOT).
EXPLORATORY OBJECTIVES:
I. To describe progression-free survival (PFS) and overall survival (OS).
II. To estimate radiographic response rate to PEP-CMV.
III. To determine the quality of the immune response by polyfunctional flow cytometry.
IV. To assess immunologic cell infiltration, antigen expression, and biomarkers for immunologic response in tumor specimens.
V. To evaluate changes in regulatory T cell (Treg) level with vaccination.
VI. Identify if the human leukocyte antigen (HLA)-2 haplotype responds better to the vaccine.
VII. To estimate the vascularity and permeability of tumors in response to PEP-CMV using perfusion magnetic resonance imaging (MRI).
OUTLINE:
Participants receive temozolomide orally (PO) starting day 1 for 5 days and tetanus-diphtheria (Td) pre-conditioning vaccination intradermally (ID) on day 20. Participants also receive PEP-CMV component A ID on days 21, 35, and 49, and then every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up every 1-3 months for up to 10 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationDuke University Medical Center
Principal InvestigatorEric Thompson
- Primary IDPro00079843
- Secondary IDsNCI-2018-00344
- ClinicalTrials.gov IDNCT03299309