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Bispecific T Cell Engager BRiTE for Patients With Grade IV Malignant Glioma (BRiTE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04903795
Recruitment Status : Not yet recruiting
First Posted : May 27, 2021
Last Update Posted : June 27, 2022
Information provided by (Responsible Party):
Duke University

Brief Summary:
This is a phase 1 study of hEGFRvIII-CD3-biscFv Bispecific T cell engager (BRiTE) in patients diagnosed with World Health Organization (WHO) grade IV malignant glioma (MG). The primary objective is to evaluate the safety of BRiTE alone and in combination with peripheral autologous T-cell infusion in patients whose MG has an EGFR (epidermal growth factor receptor) variant III (EGVRvIII) mutation.

Condition or disease Intervention/treatment Phase
Malignant Glioma Glioblastoma Drug: hEGFRvIII-CD3 (BRiTE) Biological: Activated Cell Therapy Phase 1

Detailed Description:
A maximum of eighteen patients will participate in this study after undergoing undergoing standard of care radiation therapy (XRT) with or without concomitant temozolomide (TMZ). Patients will undergo a leukapheresis to generate autologous lymphocytes that may be infused prior to BRiTE injection, pending tolerance of the BRiTE only injection. For newly diagnosed patients, leukapheresis will occur either before initiating radiation therapy or after completing radiation therapy, but before initiating adjuvant temozolomide. After completion of a minimum of six cycles of adjuvant temozolomide, or at first progression, eligible patients will receive a bolus BRiTE injection followed by a 14-day safety monitoring period. If no dose limiting toxicity (DLT) or unacceptable toxicity occurs within 14 days, patients will receive an infusion of activated cell therapy (ACT) derived from autologous lymphocytes immediately followed by a second bolus BRiTE injection.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of hEGFRvIII-CD3 Bi-scFv (BRiTE) in Patients With WHO Grade IV Malignant Glioma
Estimated Study Start Date : May 2023
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: hEGFRvIII-CD3 (BRiTE) with and without peripheral autologous T-cell (ACT) infusion
Four escalating doses of BRiTE are planned: #1: 57.0 ng/kg, #2: 570.0 ng/kg, #3: 5700.0 ng/kg, and #4: 57000.0 ng/kg. With the second injection of BRiTE, patients will each receive 3 x 10^7 T-cells per kg.
Bispecific T cell engager possessing one effector binding arm specific for the epsilon subunit of CD3 (a signaling molecule complex associated with the T cell receptor on T cells) while the opposing target-binding arm is directed against the hEGFRvIII epitope that is differentially expressed on the surface of tumor cells
Other Name: BRiTE

Biological: Activated Cell Therapy
Autologous activated human T cells obtained via leukapheresis
Other Name: ACT

Primary Outcome Measures :
  1. Dose-limiting toxicity (DLT) [ Time Frame: Begins when first BRiTE injection is given and goes through 28 days after the 2nd BRiTE injection ]
    Proportion of patients with DLT within each dose level

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 7 weeks ]
    ORR per modified Response Assessment in Neuro-Oncology Criteria (RANO)

  2. Pharmacokinetic (PK) of BRiTe observed during the first injection of BRiTE as measured by time (in minutes) [ Time Frame: 96 hours post BRiTE injection ]
    Time for the concentration of BRITE to reach half of the level initially administered

  3. Pharmacokinetic (PK) of BRiTe administered with ACT as measured by time (in minutes) [ Time Frame: 96 hours post BRiTE injection ]
    Time for the concentration of BRITE to reach half of the level initially administered

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  • Age ≥ 18 years old
  • Pathologically documented supratentorial WHO grade IV malignant glioma with an EGFRvIII mutation confirmed by Caris (at most recent diagnosis)

    1. If patient is newly diagnosed, the patient must have completed standard of care radiation therapy (3 or 6 week courses are accepted) with or without temozolomide. i. Patients with methylated MGMT promoter status need to initiate or complete 6 cycles of adjuvant temozolomide to be eligible. ii. Patients with an unmethylated MGMT promoter status do not need to initiate or complete adjuvant temozolomide to be eligible
    2. If patient is at first progression, the patient must have radiographic evidence of progression and completed a standard of care regimen of radiation therapy with or without chemotherapy and initiated adjuvant chemotherapy. Note: Imaging must be completed within 14 days of enrollment.
    3. Patients who progress during XRT or within 4 weeks after completion of XRT are not eligible.
  • Karnofsky Performance Score (KPS) ≥ 70%
  • Absolute neutrophil count (ANC) ≥ 1000/mm3
  • Platelet count ≥ 100,000
  • Hemoglobin ≥ 9.0 g/dL
  • Creatinine ≤ 1.2 x normal range
  • Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Total bilirubin ≤ 2 x ULN (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.))
  • For women of childbearing potential: negative serum pregnancy test within 1 week of 1st BRiTE injection.

Exclusion Criteria:

  • Women who are pregnant of breastfeeding
  • History or evidence of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) not associated with any antitumor surgery within 6 months before enrollment
  • Known hypersensitivity to immunoglobulins or to any other component of the BRiTE
  • Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for > 2 years before screening
  • Infection requiring intravenous antibiotics that was completed < 1 week of study enrollment (day 1) with the exemption of prophylactic antibiotics for long line insertion or biopsy
  • Known positive test for human immunodeficiency virus (HIV)
  • Known active hepatitis B or C infection
  • Toxicities from prior antitumor therapy have not resolved to CTCAE version 5 grade 1 (with the exception of adverse events reflecting myelosuppression such as neutropenia, anemia, or thrombocytopenia), or to levels dictated in the eligibility criteria. Exceptions include: alopecia or toxicities from prior antitumor therapy that are considered irreversible (defined as having been present and stable for > 2 months) are allowed if they are not otherwise described in the exclusion criteria
  • Patients on corticosteroids ≥ 2 mg dexamethasone daily or equivalent within 14 days of 1st BRiTE injection
  • Females of reproductive potential and males who are unwilling to practice an acceptable method(s) of effective birth control while on study through 1 week (5 half-lives) after receiving the last dose of study drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04903795

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Contact: Mustafa Khasraw, MBChB, MD, FRCP, FRACP 9196845301
Contact: Stevie Threatt, BA 9196845301

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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Contact: Mustafa Khasraw, MBChB, MD, FRCP, FRACP    9196845301   
Contact: Stevie Threatt, BA    9196845301   
Principal Investigator: Mustafa Khasraw, MBChB, MD, FRCP, FRACP         
Sponsors and Collaborators
Duke University
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Principal Investigator: Mustafa Khasraw, MBChB, MD, FRCP, FRACP Duke University
Additional Information:
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Responsible Party: Duke University Identifier: NCT04903795    
Other Study ID Numbers: Pro00108079
First Posted: May 27, 2021    Key Record Dates
Last Update Posted: June 27, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Duke University:
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue