Clinical Trials /

Monocyte Antigen Carrier Cells for Newly Diagnosed GBM

NCT04741984

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: Pro00105363
  • SECONDARY ID: 5P01CA225622
  • NCT ID: NCT04741984

Conditions

  • Glioblastoma
  • Glioma, Malignant

Interventions

DrugSynonymsArms
MT-201-GBM monocyte vaccineMT-201-GBM monocyte vaccine

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • MT-201-GBM monocyte vaccine

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥18 years of age

          -  Glioblastoma patient with definitive resection prior to enrollment, with residual
             radiographic contrast enhancement on most recent computed tomography (CT) or magnetic
             resonance imaging (MRI) of <1 cm in maximal diameter in any axial plane

          -  Karnofsky Performance Status (KPS) score ≥ 70

          -  MGMT promoter unmethylated (Determined by Caris Life Science pyrosequencing)

          -  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; only hormonal], sexual
             abstinence or vasectomized partner) during the trial and 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 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 [only
             hormonal], sexual abstinence or prior vasectomy) during the trial and for a period of
             > 6 months following the last administration of trial drugs.

        Exclusion Criteria:

          -  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
             (diethylene triamine pentaacetic 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

          -  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

               -  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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of MT-201-GBM
Time Frame:1 month after first infusion
Safety Issue:
Description:Dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate of 0.25.

Secondary Outcome Measures

Measure:Percentage of patients with a dose-limiting toxicity (DLT) during DLT observation period within each dose level
Time Frame:1 month after first infusion
Safety Issue:
Description: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.
Measure:Median Overall Survival (OS)
Time Frame:2 years
Safety Issue:
Description:Survival from start of MT-201-GBM
Measure:Median Progression Free Survival (PFS)
Time Frame:2 years
Safety Issue:
Description:Time to first recurrence after start of MT-201-GBM
Measure:pp65 T-cell Immune Response After Each Infusion Compared to Baseline
Time Frame:2 weeks after third infusion
Safety Issue:
Description:Mean (or median) change from baseline to peak levels within each dose level for IFN gamma, granzyme-B, and fluorospot

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Michael Gunn

Trial Keywords

  • DEMAND
  • Desjardins
  • Pro00105363
  • Glioblastoma
  • Vaccine
  • Duke

Last Updated

February 5, 2021