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GlioblastomaPhase 1DEMANDNCT04741984

Monocyte Antigen Carrier Cells for Newly Diagnosed GBM

A Phase 1 study testing MT-201-GBM monocyte vaccine in people with Glioblastoma and Glioma, Malignant, run by Michael Gunn.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The primary purpose of this study is to determine the maximum tolerated dose (MTD) of MT-201-GBM (pp65CMV antigen monocytes) that will be administered to patients newly diagnosed with a type of brain tumor called glioblastoma (GBM) that has an unmethylated MGMT (O[6]-methylguanine-DNA methyltransferase) (MGMT) gene… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma, Glioma, Malignant
What is being tested?
MT-201-GBM monocyte vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Aug 2023to Nov 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years of age;
  • Newly diagnosed glioblastoma patient with definitive resection prior to enrollment, with residual radiographic contrast enhancement on most recent magnetic resonance imaging (MRI) of <1 cm in maximal diameter in any axial plane;
  • Able to receive SOC XRT/TMZ for approximately 6 weeks duration and of more than 54GY;
  • MRI post XRT does not show progressive disease outside the radiation field;
  • Karnofsky Performance Status (KPS) score ≥ 70%;
  • MGMT promoter unmethylated (Determined by Caris Life Science pyrosequencing);
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  • Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,000 cells/µl, platelets ≥ 100,000 cells/µl prior to starting TMZ cycle 1 (patient must meet these criteria within 4 weeks after the end of XRT/TMZ to be eligible);
  • Serum creatinine ≤ 3 times institutional upper limit of normal (ULN) for age, serum aspartate aminotransferase (AST) ≤ 3 times institutional ULN for age;
  • Bilirubin ≤ 1.5 times ULN prior to starting TMZ cycle 1 (Exception: Patient has known Gilbert's Syndrome or patient has suspected Gilbert's Syndrome, for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
  • Signed informed consent approved by the Institutional Review Board (IRB);
  • 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 [IUD], sexual abstinence or vasectomized partner) during the trial and for a period of at least 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 a negative serum pregnancy test within 48 hours prior to first study treatment.
  • 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, sexual abstinence or prior vasectomy) during the trial and for a period of at least 6 months following the last administration of trial drugs.

Who cannot join

  • Pregnant or breast-feeding;
  • Women of childbearing potential and 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-DTPA (diethylenetriamine penta-acetic acid);
  • Patients who cannot undergo MRI;
  • Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of multifocal disease, or leptomeningeal disease;
  • Patients who cannot tolerate TMZ;
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  • Severe, active comorbidity, including any of the following:
  • 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 HIV positive status, Hepatitis B, Hepatitis C;
  • 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 (Treatment with tamoxifen or aromatase inhibitors or other hormonal therapy that may be indicated in prevention of prior cancer disease recurrence are not considered current active treatment.)
  • Current, recent (within 4 weeks of the administration of this study agent), or planned participation in an experimental drug study;
  • Patients are not permitted to have had any other conventional therapeutic intervention other than steroids prior to enrollment outside of standard of care chemotherapy and radiation therapy. Patients who receive previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies will be excluded.
  • Known history of autoimmune disease (with the exceptions of medically-controlled hypothyroidism and Type I Diabetes Mellitus);

About this study

Official title: The DEMAND Study: Dose Escalation Study of Monocyte Antigen Carrier Cells for Newly Diagnosed Glioblastoma With Unmethylated MGMT Gene Promoter

The primary purpose of this study is to determine the maximum tolerated dose (MTD) of MT-201-GBM (pp65CMV antigen monocytes) that will be administered to patients newly diagnosed with a type of brain tumor called glioblastoma (GBM) that has an unmethylated MGMT (O[6]-methylguanine-DNA methyltransferase) (MGMT) gene promoter.

Read the detailed description

The investigational vaccine (MT-201-GBM) in this study is made from a type of immune cell called monocytes, which have been engineered to express a cytomegalovirus (CMV) protein.

The monocyte vaccines are made from the patient's own cells, which are collected through a procedure called leukapheresis. During leukapheresis, the patient's blood is collected into a machine that removes white blood cells and then returns the remainder of the blood back to the individual. The leukapheresis procedure is not typically associated with any discomfort or pain. The white blood cells collected from leukapheresis are used to generate the patient's monocyte vaccine. After leukapheresis, patients receive standard radiation therapy combined with temozolomide for about 6 weeks, followed by one cycle of temozolomide for 21 days. About 2 days later, patients will receive the first monocyte vaccine, followed by 2 more monocyte vaccines every 4 weeks.

Being tested
MT-201-GBM monocyte vaccine
Keywords
DEMAND, Desjardins, Pro00105363, Glioblastoma, Vaccine, Duke, Gunn, 20211706
Medical subject headings
Glioblastoma, Glioma

What participants receive

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

  • MT-201-GBM monocyte vaccineBiological

    monocytes isolated from patient's leukapheresis loaded with CMV pp65-LAMP (Lysosomal-associated Membrane Protein) mRNA (Messenger Ribonucleic Acid)

Study groups in NCT04741984
Study groupRoleWhat they receive
MT-201-GBM monocyte vaccineExperimentalpp65 monocyte vaccines (MT-201-GBM) - cohorts of patients will receive increasing doses (dose escalation) of MT-201-GBM followed by a dose expansion cohort at the maximum tolerated dose. Patients will receive a total of 3 intravenous vaccines every 4 weeks after completing standard radiation therapy (XRT) and temozolomide (TMZ) and a single course of dose-intensified TMZ.
Receives: Biological: MT-201-GBM monocyte vaccine

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of MT-201-GBM

    Dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate of 0.25.

    Measured: 1 month after first infusion

  2. pp65 T-cell Immune Response After 2 Weeks Post Infusion Three Compared to Baseline

    Mean (or median) change from baseline within each dose level for IFN gamma, granzyme-B, and fluorospot

    Measured: 2 weeks after third infusion

Secondary outcomes (4)
  1. Percentage of patients with a dose-limiting toxicity (DLT) during DLT observation period within each dose level

    To assess safety and tolerability of MT-201-GMB, the percentage of patients with a dose-limiting toxicity (DLT) during the DLT observation period within each dose level will be estimated.

    Measured: 1 month after first infusion

  2. Median Overall Survival (OS)

    Survival from start of MT-201-GBM

    Measured: 2 years

  3. Median Progression Free Survival (PFS)

    Time to first recurrence after start of MT-201-GBM

    Measured: 2 years

  4. pp65 T-cell Immune Response After Each Infusion Compared to Baseline

    Mean (or median) change from baseline to peak levels within each dose level for IFN gamma and ELISpot

    Measured: 2 weeks after third infusion

Timeline

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

  1. First posted5 Feb 2021
  2. Study startAug 2023 (estimated)
  3. Primary completionMay 2025 (estimated)
  4. Study completionNov 2025 (estimated)

Why it stopped: Due to need to proceed with procedural changes with goals of improving the technical and economic feasibility.

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04741984
Sponsor's protocol ID
Pro00105363
Other IDs
5P01CA225622
Acronym
DEMAND
Status last verified
May 2023
First submitted
1 Feb 2021
Last updated
15 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MT-201-GBM monocyte vaccine in people with Glioblastoma and Glioma, Malignant, run by Michael Gunn.

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 12 inclusion and 20 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: withdrawn, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Maximum Tolerated Dose (MTD) of MT-201-GBM (time frame: 1 month after first infusion). 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 15 May 2023.

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