Mechanism of Resistance to GNC-038 in Relapsed and Refractory Diffuse Large B-cell Lymphoma

Sponsor
Ruijin Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05189782
Collaborator
(none)
15
Enrollment
19.9
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is an exploratory study embedded in the Phase Ib/II clinical trial of CD3 x 4-1BB x CD19 x PD-L1 tetra-specific T cell engager GNC-038 in relapsed and refractory diffuse large B-cell lymphoma initiated by the corresponding pharmaceutical company. By measuring immune cell components and their functional phenotypes in peripheral blood and tumor tissues before and after the subject's medication, this study aims is to identify key immune cell populations and immune molecules which play an important role in response or resistance to GNC-038 treatment, so as to optimize drug design and develop combination therapies to improve treatment efficacy.

Condition or DiseaseIntervention/TreatmentPhase

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    15 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Mechanism of Resistance to GNC-038,a Tetra-specific T Cell Engager, in Relapsed and Refractory Diffuse Large B-cell Lymphoma
    Anticipated Study Start Date :
    Feb 1, 2022
    Anticipated Primary Completion Date :
    Oct 1, 2022
    Anticipated Study Completion Date :
    Oct 1, 2023

    Arms and Interventions

    ArmIntervention/Treatment
    Subjects of the GNC-038 clinical trial (1)

    Patients enrolled in the GNC-038 Phase Ib/II clinical trial.

    Non-malignant controls (2)

    Patients who have tonsillectomy due to obstructive sleep apnea and hyponea syndrome.

    Outcome Measures

    Primary Outcome Measures

    1. The abundance of immune cell subtypes within tumor microenvironment measured by scRNA-Seq. [In Group 1: change from the screening period to treatment Day 28 or 56; change from the screening period to disease relapse or progression which is assessed up to 12 months. In Group 2: immediately following tonsil resection.]

      Core needle biopsies of lymph node lesions (in Group 1) or normal tonsil tissues (in Group 2) will be collected, and 5' end single-cell RNA plus single-cell T cell receptor (TCR) sequencing will be performed. The abundance of immune cell subtypes will be estimated from the above data.

    2. The abundance and phenotypes of peripheral blood T cell subtypes measured by CyTOF. [In Group 1: change from the screening period to treatment Day 28 or 56; change from the screening period to disease relapse or progression which is assessed up to 12 months. In Group 2: within a week before tonsil resection.]

      Peripheral blood mononuclear cells will be collected and mass cytometry by the time-of-flight (CyTOF) will be performed to analyze a panel of T cell subtyping and functional surface molecules.

    Secondary Outcome Measures

    1. Tumor cytogenetic and molecular genetic abnormalities. [During screening period, at treatment Day 28 or 56, and at disease relapse or progression which is assessed up to 12 months.]

      In Group 1, core needle biopsies of lymph node lesions will be collected, and whole exome sequencing will be performed to detect tumor cytogenetic and molecular genetic abnormalities. Peripheral blood mononuclear cells will also be collected and sequenced as healthy tissue reference.

    2. Tumor gene expression profiles. [In Group 1: during screening period, at treatment Day 28 or 56, and at disease relapse or progression which is assessed up to 12 months. In Group 2: immediately following tonsil resection.]

      In Group 1, core needle biopsies of lymph node lesions will be collected, and bulk RNA sequencing will be performed to analyze gene expression profiles of tumors.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Inclusion Criteria:

    For Group 1, the selection criteria are firstly concordant with those of the corresponding clinical trial. On this basis, the additional selection criteria for in this study are:

    • Lymph node lesions with long diameter ≥ 2cm.

    • Subjects have the ability and willingness to follow the visit, biosample collection and other research-related processes prescribed by the research program and to sign informed consent forms.

    For Group 2, the selection criteria are:
    • The subject is able to understand the informed consent form, and voluntarily participates and signs the informed consent form;

    • Age between 18 and 80;

    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 points.

    Exclusion Criteria:

    For Group 1, the exclusion criteria are totally concordant with those of the corresponding clinical trial. There is no additional exclusion criteria for this study.

    For Group 2, the exclusion criteria are:
    • History of past or present malignant diseases;

    • Patients with active autoimmune diseases, or patients with a history of autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's granulomatosis, polyvascular inflammation granuloma, Grave's disease, rheumatoid arthritis, pituitary inflammation, ophthalmic pigmentitis, autoimmune hepatitis, systemic sclerosis, Hashimoto thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain- Barre syndrome), etc.;

    • Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection (HBsAg-positive or HBcAb-positive, HBV-DNA test positive), hepatitis C virus infection (HCV antibody-positive and HCV-RNA test positive), EB virus infection (EBV-DNA test positive), cytomegalovirus infection (CMV-DNA test positive) or herpes simplex virus infection (HSV-DNA test positive);

    • Pregnant or nursing women;

    • Previous organ transplants or allogeneic hematopoietic stem cell transplants;

    • Under treatment of immunosuppressants, including but not limited to cyclosporine, tacrolimus, corticosteroids, etc., within 1 month prior to sampling;

    • Fever (temperature >37.5 ℃) within 1 month prior to sampling, or using antibiotics due to respiratory, gastrointestinal, urinary tract infections, etc.;

    • Other situations in which the researchers consider it inappropriate for the patient to participate in this study.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Ruijin Hospital

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Zhao Weili, First Deputy Director of Shanghai Institute of Hematology, Ruijin Hospital
    ClinicalTrials.gov Identifier:
    NCT05189782
    Other Study ID Numbers:
    • TRANS001-TeTE
    First Posted:
    Jan 13, 2022
    Last Update Posted:
    Jan 13, 2022
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 13, 2022