Symptoms and General Pathology

All Conditions

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Nervous System Diseases

Infections

Nutritional and Metabolic Diseases

Rare Diseases

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Glioblastoma

Glioma

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Diphtheria

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Tetanus

Tetany

Disease Attributes

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Tumor, Childhood

Neuroepithelioma

All Drugs and Chemicals

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Vaccines

Molgramostim

Sargramostim

Immunologic Factors

CMV-DCs are autologous dendritic cells derived from peripheral blood mononuclear cells (PBMCs) loaded with ribonucleic acid (RNA) encoding the human CMV matrix protein pp65 as a fusion protein with the full-length LAMP protein (pp65-flLAMP) plus GM-CSF and Td vaccine as adjuvants.

CMV-DCs are autologous dendritic cells derived from PBMCs loaded with RNA encoding the human CMV matrix protein pp65 as a fusion protein with the full-length LAMP protein (pp65-flLAMP) plus GM-CSF.

CMV-DCs with GM-CSF

Patients will receive preconditioning with Td in the right groin, and approximately 6-24 hours later, they will receive their first CMV-DC vaccination. Patients will also receive Td preconditioning approximately 6-24 hours prior to their 4th vaccine and subsequent vaccines, if any.

Td (tetanus toxoid)

Daniel Landi, MD

The purpose of this study is to determine the feasibility and safety of administering CMV RNA-pulsed dendritic cells (DCs), also known as CMV-DCs, to children and young adults up to 35 years old with nWHO Grade IV glioma, recurrent malignant glioma, or recurrent medulloblastoma. Evidence for efficacy will also be sought. This will be a phase 1 study evaluating CMV-DC administration with tetanus toxoid (Td) preconditioning and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) adjuvant in children and young adults up to 35 years old with WHO grade IV glioma, recurrent malignant glioma, or recurrent medulloblastoma. This safety study will enroll a maximum of 10 patients.

Participants in this study will undergo a leukapheresis procedure in which blood is collected into a machine that removes white blood cells and then returns the remainder of the blood back to the individual. The white blood cells removed from the blood are used to make the participant's study vaccine. Newly diagnosed patients will undergo standard radiation therapy (RT) with or without temozolomide after leukapheresis. If a patient has been diagnosed with a Grade IV glioma or recurrence of either malignant glioma or medulloblastoma, the study doctor may recommend "bridge therapy" after leukapheresis. Bridge therapy is approved or standard therapy for the tumor intended to bridge the time without the study drugs, dose-intensified temozolomide (DI-TMZ) or CMV-DC vaccine. All participants will undergo a cycle of "dose-intensified" temozolomide. Participants will receive Td pre-conditioning given as a shot in the right leg, six to 24 hours before receiving their 1st vaccine, which is also given as shots in the legs. If more than one vaccine is made, vaccines #2 and #3 will occur at 2-week intervals after the 1st vaccine. After the 3rd vaccine, there will be 4 weeks between vaccines for as many vaccines as the study team can prepare from the participant's leukapheresis.

Please note data collection will continue to occur outside of the defined primary outcomes for 2 exploratory objectives- describing changes in T cell response to CMV-DC vaccination and describing overall and progression-free survival of patients enrolled on the study. The percent change in pp65-specific T cell responses will be calculated from a pre-chemotherapy baseline, post-chemotherapy baseline, 1 week after Vaccine #3, and 1 week after final vaccine. Progression-free survival is defined as the time between starting DI TMZ and disease progression. Patients will be followed for overall survival for up to 3 years.

Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients and Young Adults With WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma

A Phase 1 Trial of CMV RNA-Pulsed Dendritic Cells With Tetanus-Diphtheria Toxoid Vaccine in Pediatric Patients and Young Adults With WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma

Percentage of patients for whom three or more vaccines can be generated from the pre-treatment leukapheresis

Percentage of patients who experience unacceptable toxicity from CMV-DC administration

Gary Archer Ph.D.

Assistant Professor of Neurosurgery

CMV-DCs With GM-CSF and Td (Tetanus Toxoid)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Principal Investigator

Percentage of Patients for Whom 3 or More Vaccines Can be Made

One eligible patient had a leukapheresis (evaluable for feasibility), but was withdrawn from the study due to clinical decline prior to receiving any treatment (not evaluable for safety).

Percentage of Patients Who Experience Unacceptable Toxicity

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients and Young Adults With WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma	NCT03615404	Glioblastoma Malignant Gliom... Medulloblastoma... Pediatric Gliob... Pediatric Brain... Pediatric Brain...	CMV-DCs with GM... Td (tetanus tox...	0 Years - 35 Years	Duke University
Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients and Young Adults With WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma	NCT03615404	Glioblastoma Malignant Gliom... Medulloblastoma... Pediatric Gliob... Pediatric Brain... Pediatric Brain...	CMV-DCs with GM... Td (tetanus tox...	0 Years - 35 Years	Duke University
Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients and Young Adults With WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma	NCT03615404	Glioblastoma Malignant Gliom... Medulloblastoma... Pediatric Gliob... Pediatric Brain... Pediatric Brain...	CMV-DCs with GM... Td (tetanus tox...	0 Years - 35 Years	Duke University
Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients and Young Adults With WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma	NCT03615404	Glioblastoma Malignant Gliom... Medulloblastoma... Pediatric Gliob... Pediatric Brain... Pediatric Brain...	CMV-DCs with GM... Td (tetanus tox...	0 Years - 35 Years	Duke University

Spots Global Cancer Trial Database for td (tetanus toxoid)