Diffuse Large B Cell Lymphoma
Conditions
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 to identify key immune cell populations and immune molecules which play an important role in resistance to GNC-038 treatment, so as to optimize drug design and develop combination therapies to improve treatment efficacy.
Interventions
None listed
Sponsors
Ruijin Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Inclusion criteria
For Group 1, the selection criteria are firstly concordant with those of the corresponding clinical trial. On this basis, additional selection criteria for 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The abundance and phenotypes of immune cell subtypes within tumor or normal tonsil tissues measured by single-cell RNA sequencing. | In Group 1: change from screening to six weeks after treatment initiation, and to disease relapse or progression assessed up to 6 months after last treatment. In Group 2: immediately following tonsil resection. | Core needle biopsies of lymph node lesions (in Group 1) or resected normal tonsil tissues (in Group 2) will be collected. 5' end single-cell RNA sequencing plus single-cell T cell receptor sequencing will be performed. The abundance and phenotypes of immune cell subtypes will be investigated using the above data. |
| The abundance and phenotypes of peripheral blood T cell subtypes measured by mass cytometry by the time-of-flight. | In Group 1: change from screening to day 22 and day 43 after treatment initiation, to 30 days after treatment ending, and to disease relapse or progression assessed up to 6 months after last treatment. In Group 2: within a week before tonsil resection. | Peripheral blood mononuclear cells will be collected and mass cytometry by the time-of-flight will be performed to analyze a panel of T cell subtyping and functional surface molecules. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor cytogenetic and molecular genetic abnormalities. | During screening, six weeks after treatment initiation, and at disease relapse or progression assessed up to 6 months after last treatment. | 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. |
| Tumor gene expression profiles. | In Group 1: during screening, six weeks after treatment initiation, and at disease relapse or progression assessed up to 6 months after last treatment. 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. |
Countries
China
Contacts
Primary ContactWeili Zhao, M.D. and Ph.D
Outcome results
None listed