Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Infections

Nutritional and Metabolic Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Diphtheria

Medulloblastoma

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

Antineoplastic Agents

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

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Prostatic Neoplasms

Esophageal Neoplasms

Vulvar Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Genital Neoplasms, Female

Vulvar Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Esophageal Cancer

Vulvar Cancer

Androgens

The research study procedures include:

* Screening for eligibility
* Three MRI scans (prior to start of standard cancer treatment, in the middle, and at the end of radiation treatment). Imaging with MRI will be performed as per disease site standards.

The research study procedures include:

* Screening for eligibility
* Three MRI scans prior to start of standard cancer treatment, in the middle, and at the end of radiation treatment). Imaging with MRI will be performed as per disease site standards.

The research study procedures include:

* Screening for eligibility
* Three MRI scans prior to start of androgen deprivation therapy, prior to the start of radiation treatment, and after radiation treatment). Imaging with MRI will be performed as per disease site standards.
* Genomic testing of biopsy sample

Imaging with MRI will be performed as per disease site standards.

MRI IMAGING

Jonathan Leeman, MD

This is a phase 1 study to determine the feasibility and utility of using serial magnetic resonance imaging (MRI) to assess treatment response during and after radiation therapy (standard of care cancer treatment) for participants with advanced esophageal cancer, glioblastoma, prostate cancer, vulvar cancer or pediatric glioma.

The research study procedures include three MRI scans (one before, one during, and one after standard of care cancer radiation therapy) for participants with advanced esophageal cancer, glioblastoma, prostate cancer, vulvar cancer or pediatric glioma.

The research study procedures include:

* Screening for eligibility
* Three MRI scans

This is a phase 1, non-randomized, open-label study evaluating feasibility of serial MRI, with an option for an expansion cohort. The optional expansion cohort is a prospective imaging registry evaluating imaging biomarkers as predictors of disease control with standard of care treatment.

This research study is a feasibility study, meaning that it is the first time that investigators at this institution are examining the process of getting multiple MRIs during radiation treatment.

The U.S. Food and Drug Administration (FDA) has cleared this MRI scanner for use.

Participants who fulfill eligibility criteria will be entered into the trial.

The research study procedures include screening for eligibility, and three MRI scans. MRI imaging will be performed as per disease site standards.

A total of 139 participants will be enrolled in this trial:

* 13 participants in the esophageal cancer cohort
* 10 participants in the initial glioblastoma cohort and 36 participants in the image registry expansion cohort
* 10 participants in the prostate cancer cohort and 50 participants in the image registry expansion cohort
* 10 participants in the vulvar cancer cohort
* 10 participants in the pediatric glioma cohort

Serial MRI Scans During Radiation Therapy

RELAY: Repeated Magnetic Resonance Imaging Examinations to Analyze and Assess Your Cancer: A Prospective Study on the Use of Serial Magnetic Resonance Imaging in the Assessment of Changes During Treatment With Radiation Therapy

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

90% lower confidence limit (LCL) on the true feasibility rate. Feasibility is defined as successfully enrolling patients, acquiring MRI data at all timepoints, identifying the target on MRI data obtained at all timepoints, and processing MRI data at all timepoints to yield pre-specified MRI-derived measurements.

Validating a previously developed predictive model to identify the most likely area of recurrence using MRI-based features.

For subprotocols studying the adaptive treatment, the secondary objective is dosimetric change in the in silico adaptive radiation therapy plans, without delivering adaptive plans in Phase I.

Dana-Farber Cancer Institute

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
Serial MRI Scans During Radiation Therapy	NCT04188535	Glioblastoma Esophageal Canc... Radiotherapy Magnetic Resona... MRI Prostate Cancer Vulvar Cancer Pediatric Gliob...	MRI IMAGING	18 Years -	Dana-Farber Cancer Institute
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
Serial MRI Scans During Radiation Therapy	NCT04188535	Glioblastoma Esophageal Canc... Radiotherapy Magnetic Resona... MRI Prostate Cancer Vulvar Cancer Pediatric Gliob...	MRI IMAGING	18 Years -	Dana-Farber Cancer Institute
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

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