PEP-CMV Vaccine and Temozolomide in Treating Patients with Glioblastoma
This phase I trial studies the side effects of peptide (PEP)-cytomegalovirus (CMV) vaccine and temozolomide and to see how well they work in treating patients with glioblastoma. Mixture of peptides from PEP-CMV vaccine may activate the immune system to help the body fight off the tumor cells in the patient's brain. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving mixture of peptides from PEP-CMV vaccine and temozolomide may work better in treating patients with glioblastoma.
Inclusion Criteria
- Histopathologically proven newly-diagnosed primary glioblastoma with complete or partial surgical resection; biopsy not acceptable
- Patients must be CMV seropositive
- The tumor must be supratentorial
- Karnofsky performance status of >= 70
- Stable or decreasing steroid dose (=< 4 mg/day) at time of post-external beam radiation therapy (XRT) adjuvant TMZ initiation; if patients are decreasing steroid use, once they are at 2 mg/day, they may be supplemented with physiologic hydrocortisone therapy (20-30 mg/day in divided doses), at the discretion of the treating oncologist
- Absolute neutrophil count (ANC) >= 1500 cells/uL
- Platelet count >= 100,000 cells/uL
- Hemoglobin >= 9.0 g/dl
- Aspartate aminotransferase (ALT)/alanine aminotransferase (AST) =< 2.5 times the upper limit of normal
- Total bilirubin =< 1.5 mg/dL
Exclusion Criteria
- Radiographic or cytologic evidence of leptomeningeal or multifocal disease at any time prior to study entry
- Prior conventional antitumor therapy, other than steroids, radiation therapy (RT) or TMZ therapy given for glioblastoma
- Pregnant or need to breast feed during the study period
- Not adhering to pregnancy prevention recommendations
- Active infection requiring intravenous antibiotics or an unexplained febrile (> 101.5 degrees Fahrenheit [F]) illness
- Immunosuppressive disease or human immunodeficiency virus infection
- Patients with unstable or severe intercurrent medical conditions such as severe heart or lung disease
- 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 within 4 weeks post XRT/TMZ is eligible
- Patients with previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies
- Prior allogeneic solid organ transplant
- Currently receiving or ever received immunosuppressive therapy for an autoimmune disorder or an organ transplant
Additional locations may be listed on ClinicalTrials.gov for NCT02864368.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To assess the safety of PEP-CMV vaccination in combination with adjuvant temozolomide (TMZ).
II. To determine the TMZ regimen that produces the highest number of T cells that specifically secrete IFNgamma by enzyme-linked immunospot (ELISPOT) in response to PEP-CMV component A.
SECONDARY OBJECTIVES:
I. To determine if tumors are CMV antigen negative by immunohistochemical analysis and microarray analysis at the time of disease progression/recurrence.
EXPLORATORY OBJECTIVES:
I. To quantitate the immune response to the PEP-CMV vaccine by pp65 ELISPOT.
II. To determine the quality of the immune response by polyfunctional flow cytometry using the pp65 peptide in PEP-CMV.
III. To evaluate if regulatory T cell (Treg) levels remain the same or decrease after vaccination.
IV. Identify if any human leukocyte antigen (HLA) haplotypes respond better to the vaccine.
V. To characterize immunologic cell infiltrate in tumors at the time of disease progression/recurrence.
VI. To describe progression free survival (PFS) and overall survival (OS) within the 2 arms.
VII. To estimate radiographic response rate to PEP-CMV in the subset of patients with residual disease.
OUTLINE: Patients are randomized to 1 of 4 arms.
ARM I: Patients receive tetanus and diphtheria toxoids adsorbed (Td) vaccine intramuscularly (IM) after signing consent. Patients receive temozolomide orally (PO) on days 1-5. Patients receive Td intradermally (ID) on day 22 of course 1. Beginning day 23, patients receive PEP-CMV component A mixed with Montanide ISA-51 ID and PEP-CMV component B mixed with sargramostim ID every 2 weeks for 3 vaccines for course 1 and on day 23 for course 2 and subsequent courses. Course 2 begins 14 days post vaccine 3 and treatment repeats every 28 days for 6-12 courses at the discretion of the treating neuro-oncologist in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after completion of last course of temozolomide, patients continue to receive PEP-CMV component A mixed with Montanide ISA-51 ID and PEP-CMV component B mixed with sargramostim ID for up to 20 vaccines in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive Td vaccine IM after signing consent. Patients receive temozolomide PO on days 1-21. Patients receive Td ID on day 22 of course 1. Beginning day 23, patients receive PEP-CMV component A mixed with Montanide ISA-51 ID every 2 weeks for 3 vaccines for course 1 and on day 23 for course 2 and subsequent courses. Course 2 begins 14 days post vaccine 3 and treatment repeats every 28 days for 6-12 courses at the discretion of the treating neuro-oncologist in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after completion of last course of temozolomide, patients continue to receive PEP-CMV component A mixed with Montanide ISA-51 ID for up to 20 vaccines in the absence of disease progression or unacceptable toxicity.
SAFETY ARM A: Patients receive Td vaccine IM after signing consent. Patients receive temozolomide PO on days 1-5. Patients receive Td ID on day 22 of course 1. Beginning day 23, patients receive PEP-CMV component A mixed with Montanide ISA-51 ID during course 1. If no hypersensitivity reaction is observed, patients then receive PEP-CMV component A mixed with Montanide ISA-51 ID and after observation for 2 hours receive PEP-CMV component B mixed with Montanide ISA-51 ID during course 2. If no hypersensitivity reaction is observed, patients continue receiving this PEP-CMV schedule and temozolomide every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of temozolomide courses, patients continue PEP-CMV every 4 weeks for up to 20 vaccines in the absence of disease progression or unacceptable toxicity.
SAFETY ARM B: Patients receive Td vaccine IM after signing consent. Patients receive temozolomide PO on days 1-5. Patients receive Td ID on day 22 of course 1. Beginning day 23, patients receive PEP-CMV component B mixed with Montanide ISA-51 ID during course 1. If no hypersensitivity reaction is observed, patients then receive PEP-CMV component B mixed with Montanide ISA-51 ID and after observation for 2 hours receive PEP-CMV component A mixed with Montanide ISA-51 ID during course 2. If no hypersensitivity reaction is observed, patients continue receiving this PEP-CMV schedule and temozolomide every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of temozolomide courses, patients continue PEP-CMV every 4 weeks for up to 20 vaccines in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 1-3 months.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationDuke University Medical Center
Principal InvestigatorDavid Michael Ashley
- Primary IDPro00034208
- Secondary IDsNCI-2017-00566
- ClinicalTrials.gov IDNCT02864368