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

NCT03615404 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Pro00092868
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma; Malignant Glioma; Medulloblastoma Recurrent; Pediatric Glioblastoma Multiforme; Pediatric Brain Tumor, Recurrent; Pediatric Brain Tumor

Keywords

glioblastoma; medulloblastoma; glioma; pediatric; recurrent; newly diagnosed; Pro00092868; Landi

Outcome Measures

Primary Outcomes (2)

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

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

  1 year

• Percentage of Patients Who Experience Unacceptable Toxicity

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

  1 year

Study Arms (1)

CMV-DCs with GM-CSF and Td (tetanus toxoid)

EXPERIMENTAL

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.

Biological: CMV-DCs with GM-CSF; Biological: Td (tetanus toxoid)

Interventions

CMV-DCs with GM-CSF BIOLOGICAL

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.

Also known as: pp65-flLAMP DC with GM-CSF

CMV-DCs with GM-CSF and Td (tetanus toxoid)

Td (tetanus toxoid) BIOLOGICAL

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.

Also known as: Tetanus and Diphtheria Toxoid

CMV-DCs with GM-CSF and Td (tetanus toxoid)

Eligibility Criteria

• Age: 0 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age requirements:
• ≤ 35 years for patients with grade IV glioma or recurrent World Health Organization (WHO) grade IV glioma
• 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 PI)
• Patients with WHO grade IV glioma who received surgery and radiation are eligible even without recurrence or progression
• Patients must have recovered from all previous treatments including chemotherapy, radiation therapy, surgery, and other immunotherapies, etc.
• a. If the patient was receiving bevacizumab at the time of enrollment, the treating oncologist has the discretion of administering and adjusting bevacizumab 10 mg/kg every 14 days. The rationale for continuing patients on bevacizumab is to prevent rebound cerebral edema commonly seen after stopping this agent.
• Laboratory Studies:
• Platelets ≥ 100,000 cells/mm3
• Creatinine ≤ 1.2 x upper limit of normal (ULN)
• Total bilirubin, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), alkaline phosphatase ≤ 2.5 x ULN
• Neutrophil count ≥ 1000 cells/mm3
• Hemoglobin ≥ 9 g/dl prior to biopsy (can be transfused)
• Able to undergo brain MRI with and without contrast
• Karnofsky Performance Status (KPS) ≥ 70 or Lansky Performance Status (LPS) ≥ 70

You may not qualify if:

• 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 intravenous (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 dose-intensified (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

Sponsors & Collaborators

• Gary Archer Ph.D.: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke
• The Preston Robert Tisch Brain Tumor Center at Duke Pediatric Program

MeSH Terms

Conditions

Glioblastoma; Glioma; Astrocytoma; Recurrence; Medulloblastoma

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; Tetanus Toxoid; Diphtheria Toxoid

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroectodermal Tumors, Primitive

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Toxoids; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Principal Investigator
• Organization: Duke University Medical Center

pedsneuronc@duke.edu

919-684-0000

Study Officials

• Daniel Landi, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Neurosurgery

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 3, 2018
• Study Start: October 5, 2018
• Primary Completion: November 19, 2019
• Study Completion: July 2, 2020
• Last Updated: January 28, 2021
• Results First Posted: January 28, 2021

Record last verified: 2021-01

Locations

US (1)