CMV-DC Vaccine in Treating Patients with Newly Diagnosed or Recurrent Glioblastoma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma
This phase I trial studies the side effects of CMV-DC vaccine and to see how well it works in treating patients with newly diagnosed glioblastoma or glioblastoma, malignant glioma, or medulloblastoma that has come back. A protein, or antigen, that is found in a common virus called cytomegalovirus (CMV), is expressed on some brain tumors. Dendritic cells (DCs) are a special type of immune system cell found in tissues of the body that boost immune responses. Vaccines made from the CMV antigen and a person's DCs may help the body build an effective immune response to kill brain tumor cells.
Inclusion Criteria
- Age requirements: * =< 18 years for patients with recurrent WHO grade III or IV glioma * 3-35 years old for patients with recurrent medulloblastoma
- Newly diagnosed or recurrent WHO grade IV glioma, recurrent WHO grade III glioma, or recurrent medulloblastoma (multifocal/disseminated disease is eligible, at the discretion of the principal investigator [PI])
- Patients must have recovered from all previous treatments, including chemotherapy, radiation therapy, surgery, and other immunotherapies, etc
- Platelets >= 100,000 cells/mm^3
- Creatinine =< 1.2 x upper limit of normal (ULN)
- Total bilirubin =< 2.5 x ULN
- Aspartate aminotransferase (AST) =< 2.5 x ULN
- Alanine aminotransferase (ALT) =< 2.5 x ULN
- Alkaline phosphatase =< 2.5 x ULN
- Neutrophil count >= 1000 cells/mm^3
- Hemoglobin >= 9 g/dl (can be transfused)
- Able to undergo brain magnetic resonance imaging (MRI) with and without contrast
- Karnofsky performance status (KPS) >= 70 or Lansky performance status (LPS) >= 70
- A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients (if 18 years old or older) or their parent(s) or guardian(s) (if younger than 18 years old) must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study
- For females of childbearing potential, negative serum pregnancy test within 48 hours of leukapheresis
- Females of childbearing potential must be willing to use acceptable contraceptive method to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug
- Males with female partners of childbearing potential must agree to practice adequate contraceptive methods throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug
- Newly diagnosed WHO grade IV glioma patients only: must be expected to complete standard of care radiation (minimum ~54 Gy)
Exclusion Criteria
- Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for >= 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
- Disease outside of the central nervous system (CNS)
- Human immunodeficiency virus (HIV), hepatitis B, or hepatitis C seropositive
- Known active infection requiring IV antibiotics or active immunosuppressive disease
- Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at initiation of radiation therapy (XRT)/ temozolomide (TMZ) * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at initiation of XRT/TMZ for newly diagnosed patients or at initiation of DI TMZ for recurrent patients * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive * Patients with autoimmune disease requiring medical management with immunosuppressant(s) * Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy * Active connective tissue disorders such as lupus or scleroderma that, in the investigator’s opinion, place the patient at high risk for radiation toxicity
- Pregnant or lactating women
- Prior allergy to TMZ, granulocyte-macrophage colony-stimulating factor (GM-CSF), gadolinium (Gd), or tetanus toxoid (Td)
- Prior history of brachial neuritis or Guillain-Barre syndrome
- Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry
- For recurrent patients only: Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used: * Patients who have received chemotherapy or bevacizumab =< 4 weeks (except for nitrosourea [6 weeks] or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide [1 week]) prior to starting the study drug unless patients have recovered from the side effects of such therapy * Patients who have received immunotherapy =< 4 weeks prior to starting the study drug unless patients have recovered from the side effects of such therapy
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03615404.
PRIMARY OBJECTIVES:
I. Determine the feasibility of producing autologous CMV-pp65-flLAMP messenger ribonucleic acid (mRNA) loaded dendritic cell vaccine (CMV-DCs) from the leukapheresis product collected from children with newly diagnosed World Health Organization (WHO) grade IV glioma, recurrent malignant glioma, or patients up to age 35 with recurrent medulloblastoma.
II. Determine the safety of intradermal administration of CMV-DCs in children with newly diagnosed WHO grade IV glioma, recurrent malignant glioma, or patients up to age 35 with recurrent medulloblastoma.
EXPLORATORY OBJECTIVES:
I. Describe changes in T cell response to CMV-DC vaccination.
II. Describe overall survival (OS) and progression free survival (PFS).
OUTLINE:
Patients receive dose intensified (DI) temozolomide orally (PO) on days 1-21 and tetanus toxoid (Td) subcutaneously (SC) on day 22. Approximately 6-24 hours later, patients also receive autologous CMV-pp65-flLAMP mRNA loaded dendritic cell vaccine intradermally (ID) then every 2 weeks for 3 doses. Beginning 4 weeks after dose 3, patients receive Td SC 6-24 before autologous CMV-pp65-flLAMP mRNA loaded dendritic cell vaccine ID every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, then periodically thereafter.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationDuke University Medical Center
Principal InvestigatorDaniel Bryce Landi
- Primary IDPro00092868
- Secondary IDsNCI-2018-02289
- ClinicalTrials.gov IDNCT03615404