Vaccine Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme (ATTAC-II)

December 19, 2024 updated by: University of Florida

ATTAC-II: A Phase II Randomized, Blinded, and Placebo-controlled Trial of CMV RNA-Pulsed Dendritic Cells With Tetanus-Diphtheria Toxoid Vaccine in Patients With Newly-Diagnosed Glioblastoma

The purpose of this research study is to determine if an investigational dendritic cell vaccine, called pp65 DC, is effective for the treatment of a specific type of brain tumor called glioblastoma (GBM) when given with stronger doses of routine chemotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Dendritic cells (DC) are involved in activating, or turning-on, your body's immune system. Your immune system helps guard your body from germs, viruses, and other threats. Although dendritic cells are very strong, the number of them in the body is not high enough to cause a powerful immune response; therefore, more DC are made in a laboratory with cells collected from an individual's blood.

In this study, we will make a vaccine that we hope will educate immune cells to target the pp65 antigen, a type of immune marker in GBM, thus resulting in what we call the pp65 DC vaccine. Use of a vaccine that activates your immune system is a type of immunotherapy. It is hoped that by giving the pp65 DC vaccine as a shot under the skin, the immune system will be activated to attack tumor cells in the brain while leaving normal cells alone.

To see if the pp65 DC vaccine is effective for the treatment of GBM, subjects will be assigned to different treatment groups. Two groups of subjects will receive the pp65 DC vaccine and one group will receive a placebo.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
175

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Orlando, Florida, United States, 32806
        • Orlando Health
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Abbreviated Inclusion Criteria:

To be assessed at study enrollment prior to standard of care chemo-radiation therapy:

  • Age ≥ 18 years.
  • Histopathologically proven newly-diagnosed de novo GBM (WHO Grade IV glioma)
  • The tumor must have a supratentorial component.
  • Must have undergone definitive surgical resection of tumor with less than approximately 3cm x 3cm residual enhancing tumor as product of longest perpendicular planes by MRI.
  • Recovery from the effects of surgery, postoperative infection, and other complications.
  • Diagnostic contrast-enhanced MRI or CT scan of the brain preoperatively and postoperatively.
  • Karnofsky Performance Status of ≥ 70.
  • Signed informed consent.
  • For females of childbearing potential, negative serum pregnancy test.
  • Women of childbearing potential and male participants must be willing to practice adequate contraception throughout the study and for at least 24 weeks after the last dose of study drug.

To be assessed prior to initiation of adjuvant TMZ:

  • Must have completed RT (targeted total dose of 59.4-60.0 Gy over ≤ 7 weeks) and concomitant TMZ (targeted dose of 75mg/m2/d for ≤ 49 days) therapy without significant toxicity that persisted over 4 weeks.
  • History & physical with neurologic examination prior to initiation of adjuvant TMZ.
  • For patients receiving steroids, daily dose must be ≤ 4 mg.
  • CBC with differential with adequate bone marrow function.
  • Adequate renal function.
  • Adequate hepatic function.

Abbreviated Exclusion Criteria:

To be verified in order to randomize subject:

  • Prior invasive malignancy unless disease free for ≥ 3 years.
  • Metastases detected below the tentorium or beyond the cranial vault and leptomeningeal involvement.
  • Recurrent or multifocal malignant gliomas.
  • HIV, Hepatitis B, or Hepatitis C seropositive.
  • Known active infection or immunosuppressive disease.
  • Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the head and neck region.
  • Prior radiotherapy to the head or neck, resulting in overlap of radiation fields.
  • Severe, active co-morbidity.
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for the entire study period.
  • Pregnant or lactating women.
  • Prior allergic reaction to temozolomide, GM-CSF 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.

To be assessed prior to initiation of adjuvant TMZ:

  • Did not start radiation therapy and temozolomide within 7 weeks of surgery.
  • Progression of disease as defined by modified RANO criteria.
  • More than 45 days after completion of radiation therapy and temozolomide

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm 1: pp65-shLAMP DC with GM-CSF and Td
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
Biological: pp65-shLAMP DC with GM-CSF
Other Names:
  • pp65-shLAMP mRNA DCs with GM-CSF
Drug: Td
All subjects will receive a Td booster before study drug dose #1. Subjects in the experimental arms will receive Td skin prep before study drug doses #3, #6, and #9.
Other Names:
  • Tetanus and Diphtheria Toxoid
Experimental: Arm 2: pp65-flLAMP DC with GM-CSF and Td
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
Drug: Td
All subjects will receive a Td booster before study drug dose #1. Subjects in the experimental arms will receive Td skin prep before study drug doses #3, #6, and #9.
Other Names:
  • Tetanus and Diphtheria Toxoid
Biological: pp65-flLAMP DC with GM-CSF
Other Names:
  • pp65-flLAMP mRNA DCs with GM-CSF
Placebo Comparator: Arm 3: unpulsed PBMC and Saline
Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
Drug: Saline
Other Names:
  • Normal Saline
Biological: unpulsed PBMC and saline
Other Names:
  • Peripheral Blood Mononuclear Cells

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Comparison of Overall Survival (OS) Between the Active Treatment Group (Arms 1 and 2) and the Control Group (Arm 3)
Time Frame: From date of first vaccine until the date of death, up to 48 months
Kaplan-Meier survival curves and the log rank test will be used to characterize and compare OS in patients who received pp65-LAMP mRNA DC vaccine (Arms 1 and 2) and in control patients (Arm 3). OS will be defined as the time between first vaccination and death and will be censored at the last follow-up if death has not occurred.
From date of first vaccine until the date of death, up to 48 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparison of Progression-free Survival Between the Active Treatment Group (Arms 1 and 2 Combined) and the Control Group (Arm 3)
Time Frame: From date of first vaccine until time disease progression or death without prior progression/recurrence, up to 48 months
Calculated as dated of first vaccine to date first progression/recurrence or death. Kaplan-Meier survival curves and the log rank test will be used to characterize and compare PFS in patients who received pp65-LAMP mRNA DC vaccine (Arms 1 and 2) and in control patients (Arm 3). PFS is defined as the time between first vaccination and first documentation of either disease progression/recurrence, or death without prior progression/recurrence.
From date of first vaccine until time disease progression or death without prior progression/recurrence, up to 48 months
ELISPOT Assay (pp65)
Time Frame: baseline, post-vaccine #3
Within patient changes from baseline to vaccine 3.
baseline, post-vaccine #3
Flow Cytometric Analysis (T Cell)
Time Frame: baseline, post-vaccine #3
Percentage of circulating cellular subsets of T cells within PBMCs.
baseline, post-vaccine #3
Cytokine Array Analysis (IFN-g)
Time Frame: baseline, post-vaccine #3
Change in concentration (pg/mL) of IFN-g as measured by multiplex array from Baseline (V1) to post-Vaccine #3.
baseline, post-vaccine #3
ELISPOT Assay (Actin)
Time Frame: baseline, post-vaccine #3
Within patient changes from baseline to vaccine 3.
baseline, post-vaccine #3
Flow Cytometric Analysis (NK Cell)
Time Frame: baseline, post-vaccine #3
Percentage of circulating cellular subsets of NK cells within PBMCs.
baseline, post-vaccine #3
Flow Cytometric Analysis (CD4.CD25 T Reg)
Time Frame: baseline, post-vaccine #3
Percentage of circulating cellular subsets of CD4.CD25 T Reg within PBMCs.
baseline, post-vaccine #3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Florida

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Duane Mitchell, MD, PhD, University of Florida
  • Principal Investigator: Maryam Rahman, MD, University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 9, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 27, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 3, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 8, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB201400697-N
  • R01CA175517 (U.S. NIH Grant/Contract)
  • OCR14127 (Other Identifier: Universiy of Florida)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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