DEMAND: Monocyte Antigen Carrier Cells for Newly Diagnosed GBM

Sponsor
Michael Gunn (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04741984
Collaborator
National Cancer Institute (NCI) (NIH)
27
1
1
36
0.7

Study Details

Study Description

Brief 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 promoter.

Condition or Disease Intervention/Treatment Phase
  • Biological: MT-201-GBM monocyte vaccine
Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
27 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The DEMAND Study: Dose Escalation Study of Monocyte Antigen Carrier Cells for Newly Diagnosed Glioblastoma With Unmethylated MGMT Gene Promoter
Anticipated Study Start Date :
Aug 1, 2022
Anticipated Primary Completion Date :
Feb 1, 2025
Anticipated Study Completion Date :
Aug 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: MT-201-GBM monocyte vaccine

pp65 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.

Biological: MT-201-GBM monocyte vaccine
monocytes isolated from patient's leukapheresis loaded with CMV pp65-LAMP (Lysosomal-associated Membrane Protein) mRNA (Messenger Ribonucleic Acid)

Outcome Measures

Primary Outcome Measures

  1. Maximum Tolerated Dose (MTD) of MT-201-GBM [1 month after first infusion]

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

  2. pp65 T-cell Immune Response After 2 Weeks Post Infusion Three Compared to Baseline [2 weeks after third infusion]

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

Secondary Outcome Measures

  1. Percentage of patients with a dose-limiting toxicity (DLT) during DLT observation period within each dose level [1 month after first infusion]

    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.

  2. Median Overall Survival (OS) [2 years]

    Survival from start of MT-201-GBM

  3. Median Progression Free Survival (PFS) [2 years]

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

  4. pp65 T-cell Immune Response After Each Infusion Compared to Baseline [2 weeks after third infusion]

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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)

Contacts and Locations

Locations

Site City State Country Postal Code
1 The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center Durham North Carolina United States 27710

Sponsors and Collaborators

  • Michael Gunn
  • National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Annick S Desjardins, MD, FRCPC, Duke University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Michael Gunn, Professor of Medicine, Duke University
ClinicalTrials.gov Identifier:
NCT04741984
Other Study ID Numbers:
  • Pro00105363
  • 5P01CA225622
First Posted:
Feb 5, 2021
Last Update Posted:
May 27, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Michael Gunn, Professor of Medicine, Duke University
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 27, 2022