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GlioblastomaPhase 2ELEVATENCT02366728

DC Migration Study for Newly-Diagnosed GBM

A Phase 2 study testing Unpulsed DCs, Td and Human CMV pp65-LAMP mRNA-pulsed autologous DCs in people with Glioblastoma and Astrocytoma, Grade IV, run by Mustafa Khasraw, MBChB, MD, FRCP, FRACP at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized phase II study will assess the impact of pre-conditioning on migration and survival among newly diagnosed glioblastoma (GBM) patients who have undergone definitive resection and completed standard temozolomide (TMZ) and radiation treatment, as well as the impact of tetanus pre-conditioning and… Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Unpulsed DCs, Td and Human CMV pp65-LAMP mRNA-pulsed autologous DCs
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
1 siteUnited States
Study dates
12 Oct 2015to 31 Oct 2020
Phase
Phase 2
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 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years of age
  • WHO Grade IV Glioma with definitive resection prior to enrollment, with residual radiographic contrast enhancing disease on the post-operative CT or Magnetic Resonance Imaging (MRI) of <1 cm in maximal diameter in any axial plane
  • MRI post radiation therapy (RT) does not show progressive disease at time of randomization
  • Karnofsky Performance Status of > 80%.
  • Hemoglobin ≥ 9.0 g/dl, Absolute Neutrophil Count ≥ 1,500 cells/µl, platelets ≥ 125,000 cells/µl
  • Serum creatinine ≤ 1.5 mg/dl, Serum Glutamic Oxaloacetic Transaminase \& bilirubin ≤ 1.5 times upper limit of normal
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  • Signed informed consent approved by the Institutional Review Board
  • Female patients must not be pregnant or breast-feeding. Female patients of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, [i.e. with a failure rate of < 1% per year] are implants, injectables, combined oral contraceptives, intra-uterine device [IUDs; only hormonal], sexual abstinence or vasectomized partner) during the trial \& for a period of > 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have negative serum pregnancy test within 48 hours prior to first study procedure (leukapheresis).
  • Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control [i.e. with a failure rate of < 1% per year] include a female partner using implants, injectables, combined oral contraceptives, IUDs [only hormonal], sexual abstinence or prior vasectomy) during the trial \& for a period of > 6 months following the last administration of trial drugs

Who cannot join

  • Pregnant or breast-feeding
  • Women of childbearing potential \& men who are sexually active and not willing/able to use medically acceptable forms of contraception
  • Patients with known potentially anaphylactic allergic reactions to gadolinium-Diethylenetriaminepentaacetic Acid
  • Patients who cannot undergo MRI or SPECT due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates)
  • Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of multifocal disease, or leptomeningeal disease
  • Severe, active comorbidity, including any of the following
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  • Unstable angina and/or congestive heart failure requiring hospitalization
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study initiation
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  • Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
  • Known Human Immunodeficiency Virus positive status
  • 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 opinion of the treating physician, may put the patient at high risk for radiation toxicity
  • Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;
  • Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
  • Patients are not permitted to have had any other conventional therapeutic intervention other than steroids prior to enrollment outside of standard of care chemotherapy \& radiation therapy. Patients who receive previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies will be excluded
  • Current, recent (within 4 weeks of the administration of this study agent), or planned participation in an experimental drug study
  • Known history of autoimmune disease (with the exceptions of medically-controlled hypothyroidism and Type I Diabetes Mellitus)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: Evaluation of Overcoming Limited Migration and Enhancing Cytomegalovirus-specific Dendritic Cell Vaccines With Adjuvant TEtanus Pre-conditioning in Patients With Newly-diagnosed Glioblastoma

This randomized phase II study will assess the impact of pre-conditioning on migration and survival among newly diagnosed glioblastoma (GBM) patients who have undergone definitive resection and completed standard temozolomide (TMZ) and radiation treatment, as well as the impact of tetanus pre-conditioning and basiliximab together on survival. After completing standard of care radiotherapy with concurrent TMZ, patients will be randomized to 1 of 3 treatment arms: 1). receive cytomegalovirus (CMV)-specific dendritic cell (DC) vaccines with unpulsed (not loaded) DC pre-conditioning prior to the 4th vaccine; 2). receive CMV-specific DC vaccines with Tetanus-Diphtheria Toxoid (Td) pre-conditioning prior to the 4th vaccine; 3). receive basiliximab infusions prior to the 1st and 2nd DC vaccines along with Td pre-conditioning prior to the 4th vaccine. A permuted block randomization algorithm using a 1:1:1 allocation ratio will be used to assign patients to a treatment arm. Randomization will be stratified by CMV status (positive, negative), with the assignment to arms I and II being double-blinded. Effective March 2017, randomization to Group III has been terminated.

Read the detailed description

A maximum of 100 patients with resected, newly-diagnosed World Health Organization (WHO) Grade IV GBM will be enrolled in this study with the expectation that approximately 79 patients will be randomized to subsequent treatment after completion of radiation treatment with concurrent temozolomide. Effective March 2017, randomization to Group III has been terminated. All consented patients will undergo a leukapheresis after resection for harvest of Peripheral Blood Lymphocytes (PBLs) for generation of DCs. Patients will then receive Radiation Therapy (RT) and concurrent TMZ at a standard targeted dose of 75 mg/m^2/d. Patients should start RT within approximately 6 weeks of surgery. Patients who experience progressive disease during radiation, are dependent on steroid supplements above physiologic levels at time of first vaccination, are unable to tolerate TMZ, or whose DCs or PBLs fail to meet release criteria will be withdrawn from the study and replaced and will not undergo repeat leukapheresis. For patients whose initial leukapheresis yields less than 3 vaccines, repeat leukapheresis may be obtained a minimum of 2 weeks from the previous leukapheresis (and may be repeated as needed) if pre-pheresis blood work is within the Apheresis Center's parameters and as long as this does not cause a significant delay in treatment for the patient.

After RT and concurrent TMZ, patients will then be randomized and begin the initial cycle of TMZ at a standard targeted dose of 150-200mg/m^2/d for 5 days at the discretion of the treating oncologist 4 (± 2) weeks after completing RT. The study cycle of TMZ comprises a targeted dose of 150-200mg/m^2/d for 5 days every 5 (± 1) weeks. All patients will receive up to a total of 10 DC vaccines given bilaterally at the groin site unless progression occurs. DC vaccines will be given intradermally (i.d.) and divided equally to both inguinal regions. DC vaccines #1-3 will be given every two weeks, thus delaying the initiation of TMZ cycle 2. Patients will then be vaccinated in conjunction with subsequent TMZ cycles every 5 (± 1) weeks for a total of 6 to 12 cycles after RT at the discretion of the treating oncologist. DCs will be given on day 21 ± 2 days of each TMZ cycle. DC vaccinations will continue during TMZ cycles up to a total of 10 unless progression occurs.

Before the first DC vaccination, all patients will receive immunization with 0.5 mL of Td intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Those assigned to Group III will receive basiliximab 20 mg infusions 1 week before the 1st and 1 week before the 2nd vaccine. At the time of the fourth DC vaccine, patients will receive pre-conditioning per the assigned group (Group I-unpulsed DCs i.d.; Group II- Td i.d.; Group III-Td i.d.). A single dose of Td toxoid (1 flocculation unit, in 0.3 milliliters (mLs) of saline for a total volume of 0.4 mLs) or 0.4 mLs of 1 x 10^6 autologous unpulsed DCs in saline will be administered to a single side of the groin, and 0.4 mLs of saline administered to the contralateral side 12-24 hours prior to the fourth DC vaccine, which is always given bilaterally at the groin site. Patients in Groups I and II will then receive 111In-labeled DCs to compare the effects of different skin preparations on DC migration followed by Single-Photon Emission Computed Tomography and Computed Tomography (SPECT/CT) imaging immediately and at 1 and 2 days after injection. Group III will not undergo migration studies. Groups I and II will be double blinded. Group III will not be blinded.

All patients will undergo leukapheresis again for immunologic monitoring with specific assessment of baseline antigen-specific cellular and humoral immune responses and further DC generations 4 (± 2) weeks after vaccine #3. Patients will be imaged bimonthly without receiving any other prescribed anti-tumor therapy. Patients will undergo an additional leukapheresis for generation of DCs if needed to continue vaccinations.

As part of standard care for these patients, upon tumor progression, participants may undergo stereotactic biopsy or resection. As this is not a research procedure consent will be obtained separately. However, if tissue is obtained, it will be used to confirm tumor progression histologically and to assess immunologic cell infiltration and pp65 antigen escape at the tumor site.

Being tested
Unpulsed DCs, Td, Human CMV pp65-LAMP mRNA-pulsed autologous DCs, 111In-labeled DCs, Temozolomide
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Unpulsed DCsBiological

    Also called Unpulsed DCs pre-conditioning

    Patients in Group I will receive 1 x 10^6 autologous unpulsed DCs in saline administered to a single side of the groin intradermally 1 day before the fourth vaccine.

  • TdBiological

    Also called Td toxoid, Td pre-conditioning

    Patients in Groups II and III will receive a single dose of Td toxoid (1 flocculation unit, Lf, in 0.4 mLs) administered to a single side of the groin given intradermally 1 day before the fourth vaccine.

  • Human CMV pp65-LAMP mRNA-pulsed autologous DCsBiological

    Also called CMV-specific dendritic cell vaccine, DCs

    2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines.

  • 111In-labeled DCsBiological

    111In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs will be labeled with 111In (50 μCi / 5 x 10^7 DCs) and given i.d. as fourth vaccine for Groups I and II only.

  • TemozolomideDrug

    Also called Temodar, TMZ

    Temozolomide is a standard chemotherapy given to all enrolled patients at a targeted dose of 150-200mg/m2/d for 5 days every 5 (± 1) weeks for a total of 6 to 12 cycles at the discretion of the treating oncologist.

  • SalineDrug

    0.4mL of saline given in the opposite groin 1 day before the fourth vaccine in all groups

  • BasiliximabDrug

    Group III will receive basiliximab infusions (20 mg I.V) 1 week before the first vaccine and 1 week before the second vaccine.

Study groups in NCT02366728
Study groupRoleWhat they receive
Group I: Unpulsed DC pre-conditioningExperimental0.4 mLs of 1 x 10^6 autologous unpulsed DCs in saline will be administered to a single side of the groin, and 0.4 mLs of saline administered to the contralateral side 1 day prior to the 4th human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine. pp65 DC Vaccine #4 is 111In-labeled DCs for migration studies.
Receives: Biological: Unpulsed DCs; Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs; Biological: 111In-labeled DCs; Drug: Temozolomide; Drug: Saline
Group II: Tetanus pre-conditioningExperimentalTetanus diptheria toxoid (Td) (1 flocculation unit) will be administered to a single side of the groin, and 0.4 mLs of saline administered to the contralateral side 1 day prior to the 4th human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine. pp65 DC Vaccine #4 is 111In-labeled DCs for migration studies.
Receives: Biological: Td; Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs; Biological: 111In-labeled DCs; Drug: Temozolomide; Drug: Saline
Group III: Basiliximab and Tetanus pre-conditioningExperimentalBasiliximab infusions prior to human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccines #1 and #2 with Td pre-conditioning (1 flocculation unit) will be administered to a single side of the groin, and 0.4 mLs of saline administered to the contralateral side 1 day prior to the 4th human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine.
Receives: Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs; Drug: Temozolomide; Drug: Saline; Drug: Basiliximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median Overall Survival

    Overall survival will be defined as the time in months between randomization and death, or last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.

    Measured: Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

  2. Percentage of 111In-labeled Dendritic Cells Migrating to the Inguinal Lymph Nodes

    Within Groups I and II only, the percentage of 111In-labeled DCs migrating to the inguinal lymph nodes from the initial injection sites in the left and right groin at 48 hours post-vaccination #4 will be calculated.

    Measured: For each patient, migration studies will occur after vaccination #4 which occurs approximately 7 months after study consent.

  3. Median Overall Survival in CMV Positive Participants

    Median overall survival will be estimated in the subset of participants that are CMV positive. Overall survival will be defined as the time in months between randomization and death, or last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.

    Measured: Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

  4. Median Overall Survival in CMV Negative Participants

    Median overall survival will be estimated in the subset of participants that are CMV negative. Overall survival will be defined as the time in months between randomization and death, or last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.

    Measured: Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

Secondary outcomes (3)

  1. Median Progression-free Survival

    Progression-free survival will be defined as the time in months between randomization and disease progression or death. Participants alive without disease progression will be censored at the time of their last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.

    Measured: Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

  2. Median Progression-free Survival in CMV Positive Participants

    Median progression-free survival will be estimated in the subset of participants that are CMV positive. Progression-free survival will be defined as the time in months between randomization and disease progression or death. Participants alive without disease progression will be censored at the time of their last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.

    Measured: Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

  3. Median Progression-free Survival in CMV Negative Participants

    Median progression-free survival will be estimated in the subset of participants that are CMV negative. Progression-free survival will be defined as the time in months between randomization and disease progression or death. Participants alive without disease progression will be censored at the time of their last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.

    Measured: Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2015 (estimated)
  2. Study start12 Oct 2015
  3. Primary completion31 Oct 2020
  4. Study completion31 Oct 2020

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02366728
Sponsor's protocol ID
Pro00054740
Acronym
ELEVATE
Status last verified
Jun 2023
First submitted
28 Oct 2014
Last updated
8 Jun 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Unpulsed DCs, Td and Human CMV pp65-LAMP mRNA-pulsed autologous DCs in people with Glioblastoma and Astrocytoma, Grade IV, run by Mustafa Khasraw, MBChB, MD, FRCP, FRACP 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 9 inclusion and 19 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 8 Jun 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 1 Feb 2022). 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?

Median Overall Survival (time frame: Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02366728.

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 8 Jun 2023.

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