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Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients With Newly Diagnosed WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma (ATTAC-P)

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ClinicalTrials.gov Identifier: NCT03615404
Recruitment Status : Active, not recruiting
First Posted : August 3, 2018
Last Update Posted : March 20, 2019
Sponsor:
Information provided by (Responsible Party):
Gary Archer Ph.D., Duke University

Brief Summary:

Enrollment in this study is being temporarily held for maintenance of the the facility that manufactures study vaccine.

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 with newly diagnosed WHO Grade IV glioma, recurrent malignant glioma, or patients up to 35 years old with 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 with newly diagnosed glioblastoma (GBM), recurrent malignant glioma, or patients up to 35 years old with recurrent medulloblastoma. This safety study will enroll a maximum of 10 patients.


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

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 is experiencing a recurrence, 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 (DI-TMZ will start about 4 weeks after completing standard RT for newly diagnosed patients and about 3 weeks after leukapheresis for recurrent patients). 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. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of CMV RNA-Pulsed Dendritic Cells With Tetanus-Diphtheria Toxoid Vaccine in Pediatric Patients With Newly Diagnosed WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma
Actual Study Start Date : October 5, 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : October 2022


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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

  2. Percentage of patients who experience unacceptable toxicity [ Time Frame: 1 year ]
    Percentage of patients who experience unacceptable toxicity from CMV-DC administration



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Ages Eligible for Study:   up to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age requirements:

    1. ≤ 18 years for patients with recurrent World Health Organization (WHO) grade III or IV glioma
    2. 3-35 years old for patients with recurrent medulloblastoma
  2. 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)
  3. Patients must have recovered from all previous treatments including chemotherapy, radiation therapy, surgery, and other immunotherapies, etc.
  4. Laboratory Studies:

    1. Platelets ≥ 100,000 cells/mm3
    2. Creatinine ≤ 1.2 x upper limit of normal (ULN)
    3. Total bilirubin, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), alkaline phosphatase ≤ 2.5 x ULN
    4. Neutrophil count ≥ 1000 cells/mm3
    5. Hemoglobin ≥ 9 g/dl prior to biopsy (can be transfused)
  5. Able to undergo brain MRI with and without contrast
  6. Karnofsky Performance Status (KPS) ≥ 70 or Lansky Performance Status (LPS) ≥ 70
  7. A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients (if 18 years old or older) or their parent(s) or guardian(s) (if younger than 18 years old) must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study.
  8. For females of childbearing potential, negative serum pregnancy test within 48 hours of leukapheresis
  9. Females of childbearing potential must be willing to use acceptable contraceptive method to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug
  10. Males with female partners of childbearing potential must agree to practice adequate contraceptive methods throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug
  11. Newly diagnosed WHO grade IV glioma patients only: must be expected to complete standard of care radiation (minimum ~54 Gray)

Exclusion Criteria:

  1. 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)
  2. Disease outside of the central nervous system (CNS)
  3. Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C seropositive
  4. Known active infection requiring intravenous (IV) antibiotics or active immunosuppressive disease
  5. Severe, active co-morbidity, defined as follows:

    1. Unstable angina and/or congestive heart failure requiring hospitalization
    2. Transmural myocardial infarction within the last 6 months
    3. Acute bacterial or fungal infection requiring intravenous antibiotics at initiation of Radiation Therapy (XRT)/Temozolomide (TMZ)
    4. 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
    5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    6. 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
    7. Patients with autoimmune disease requiring medical management with immunosuppressant(s)
    8. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy
    9. Active connective tissue disorders such as lupus or scleroderma that, in the investigator's opinion, place the patient at high risk for radiation toxicity
  6. Pregnant or lactating women
  7. Prior allergy to TMZ, GM-CSF, gadolinium (Gd), or Td
  8. Prior history of brachial neuritis or Guillain-Barré syndrome
  9. Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry
  10. For recurrent patients only: Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used:

    1. Patients who have received chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea (6 weeks) or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)] prior to starting the study drug unless patients have recovered from the side effects of such therapy
    2. Patients who have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from the side effects of such therapy

Information from the National Library of Medicine

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


Locations
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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Gary Archer Ph.D.
Investigators
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Principal Investigator: Daniel Landi, MD Duke University

Additional Information:
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Responsible Party: Gary Archer Ph.D., Assistant Professor of Neurosurgery, Duke University
ClinicalTrials.gov Identifier: NCT03615404     History of Changes
Other Study ID Numbers: Pro00092868
First Posted: August 3, 2018    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gary Archer Ph.D., Duke University:
glioblastoma
medulloblastoma
glioma
pediatric
recurrent
newly diagnosed
Pro00092868
Landi

Additional relevant MeSH terms:
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Glioblastoma
Glioma
Brain Neoplasms
Medulloblastoma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroectodermal Tumors, Primitive
Vaccines
Sargramostim
Immunologic Factors
Physiological Effects of Drugs