Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients and Young Adults With WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma
Condition: Glioblastoma; Malignant Glioma; Medulloblastoma Recurrent; Pediatric Glioblastoma Multiforme; Pediatric Brain Tumor, Recurrent; Pediatric Brain Tumor
MeSH terms: Glioblastoma; Glioma; Brain Neoplasms; Medulloblastoma; Recurrence
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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.
    

Intervention name(s): CMV-DCs with GM-CSF; Td (tetanus toxoid)
Intervention type(s): Biological; Biological
Intervention description(s): 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.; 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 intervention name(s): pp65-flLAMP DC with GM-CSF; Tetanus and Diphtheria Toxoid
Intervention MeSH terms: Molgramostim; Sargramostim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: glioblastoma; medulloblastoma; glioma; pediatric; recurrent; newly diagnosed; Pro00092868; Landi