Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients and Young Adults With WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma (ATTAC-P)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03615404|
Recruitment Status : Active, not recruiting
First Posted : August 3, 2018
Last Update Posted : May 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Malignant Glioma Medulloblastoma Recurrent Pediatric Glioblastoma Multiforme Pediatric Brain Tumor, Recurrent Pediatric Brain Tumor||Biological: CMV-DCs with GM-CSF Biological: Td (tetanus toxoid)||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||October 5, 2018|
|Actual Primary Completion Date :||November 19, 2019|
|Estimated Study Completion Date :||August 2022|
Experimental: CMV-DCs with GM-CSF and Td (tetanus toxoid)
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
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.
Other Name: pp65-flLAMP DC with GM-CSF
Biological: Td (tetanus toxoid)
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.
Other Name: Tetanus and Diphtheria Toxoid
- Percentage of patients for whom 3 or more vaccines can be made [ Time Frame: 1 year ]Percentage of patients for whom three or more vaccines can be generated from the pre-treatment leukapheresis
- Percentage of patients who experience unacceptable toxicity [ Time Frame: 1 year ]Percentage of patients who experience unacceptable toxicity from CMV-DC administration
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03615404
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Daniel Landi, MD||Duke University|