GlioblastomaPhase 1ATTAC-PNCT03615404
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 study testing CMV-DCs with GM-CSF and Td (tetanus toxoid) in people with Glioblastoma and Malignant Glioma, run by Gary Archer Ph.D. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 35 years
- Conditions the study is for
- Glioblastoma, Malignant Glioma, Medulloblastoma Recurrent
- What is being tested?
- CMV-DCs with GM-CSF and Td (tetanus toxoid)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Oct 2018to 2 Jul 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age requirements:
- ≤ 35 years for patients with grade IV glioma or recurrent World Health Organization (WHO) grade IV glioma
- 3-35 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.
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- 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
- 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.
- For females of childbearing potential, negative serum pregnancy test within 48 hours of leukapheresis
- 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
- 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
- Newly diagnosed WHO grade IV glioma patients only: must be expected to complete standard of care radiation (minimum ~54 Gray)
Who cannot join
- 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
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- 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
- Prior allergy to TMZ, GM-CSF, gadolinium (Gd), or Td
- Prior history of brachial neuritis or Guillain-Barré syndrome
- Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry
- Patients receiving > 0.1mg/kg or 4mg/day dexamethasone or equivalent
- 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:
- 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. 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.
- Patients who have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from the side effects of such therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
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
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.
Read the 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.
- Conditions
- Glioblastoma, Malignant Glioma, Medulloblastoma Recurrent, Pediatric Glioblastoma Multiforme, Pediatric Brain Tumor, Recurrent, Pediatric Brain Tumor
- Being tested
- CMV-DCs with GM-CSF, Td (tetanus toxoid)
- Keywords
- glioblastoma, medulloblastoma, glioma, pediatric, recurrent, newly diagnosed, Pro00092868, Landi
- Medical subject headings
- Glioblastoma, Glioma, Astrocytoma, Recurrence, Medulloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV-DCs with GM-CSFBiological
Also called pp65-flLAMP DC 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.
Td (tetanus toxoid)Biological
Also called Tetanus and Diphtheria 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: CMV-DCs with GM-CSF; Biological: Td (tetanus toxoid) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year
Percentage of Patients Who Experience Unacceptable Toxicity
Percentage of patients who experience unacceptable toxicity from CMV-DC administration
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2018
- Study start5 Oct 2018
- Primary completion19 Nov 2019
- Study completion2 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gary Archer Ph.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gary Archer Ph.D., Duke University
- Investigators
- Daniel Landi, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03615404
- Sponsor's protocol ID
- Pro00092868
- Acronym
- ATTAC-P
- Status last verified
- Jan 2021
- First submitted
- 30 Jul 2018
- Last updated
- 28 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03615404
- Acronym / sponsor ID
- ATTAC-P / Pro00092868
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Gary Archer Ph.D.University, hospital or other
- Study start
- 5 Oct 2018 (actual)
- Primary completion
- 19 Nov 2019 (actual)
- Study completion
- 2 Jul 2020 (actual)
- First posted
- 3 Aug 2018 (actual)
- Results
- Posted 28 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CMV-DCs with GM-CSF and Td (tetanus toxoid) | Experimental | Biological: CMV-DCs with GM-CSF, Biological: 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. |
Who may qualify
- Ages
- 0 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Age requirements:
- 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.
- Laboratory Studies:
Key exclusion criteria (22 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CMV-DCs with GM-CSFAlso: pp65-flLAMP DC with GM-CSFCMV-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. | Biological | CMV-DCs with GM-CSF and Td (tetanus toxoid) |
| Td (tetanus toxoid)Also: Tetanus and Diphtheria ToxoidPatients 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. | Biological | CMV-DCs with GM-CSF and Td (tetanus toxoid) |
Primary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Preston Robert Tisch Brain Tumor Center at DukeLink provided by the sponsor.
- The Preston Robert Tisch Brain Tumor Center at Duke Pediatric ProgramLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Landi, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CMV-DCs with GM-CSF and Td (tetanus toxoid) in people with Glioblastoma and Malignant Glioma, run by Gary Archer Ph.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients for Whom 3 or More Vaccines Can be Made (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2021.