Monocyte Antigen Carrier Cells for Newly Diagnosed GBM

NCT04741984 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: Pro001053635P01CA225622
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Glioblastoma; Glioma, Malignant

Keywords

DEMAND; Desjardins; Pro00105363; Glioblastoma; Vaccine; Duke; Gunn; 20211706

Outcome Measures

Primary Outcomes (2)

• 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.

  1 month after first infusion

• 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

  2 weeks after third infusion

Secondary Outcomes (4)

• Percentage of patients with a dose-limiting toxicity (DLT) during DLT observation period within each dose level

  1 month after first infusion

• Median Overall Survival (OS)

  2 years

• Median Progression Free Survival (PFS)

  2 years

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

  2 weeks after third infusion

Study Arms (1)

MT-201-GBM monocyte vaccine

EXPERIMENTAL

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

Interventions

MT-201-GBM monocyte vaccine BIOLOGICAL

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

MT-201-GBM monocyte vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Michael Gunn: lead
• National Cancer Institute (NCI): collaborator

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke
• Duke Health

MeSH Terms

Conditions

Glioblastoma; Glioma

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Annick S Desjardins, MD, FRCPC

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 5, 2021
• Study Start: August 1, 2023
• Primary Completion: May 1, 2025
• Study Completion: November 1, 2025
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share