Leukemia, Chronic Lymphocytic, Richter Syndrome
Conditions
Keywords
Epcoritamab, Pharmacodynamic, Tumor Microenvironment, Clonal Dynamics, Biomarker
Brief summary
This correlative study aims to understand the pharmacodynamic effects and clonal dynamics in response to epcoritamab by obtaining and analyzing lymph node, bone marrow, and blood samples from subjects enrolled in GCT3013-03 trial sponsored by Genmab at NIH. Samples will be collected before and at multiple time points during treatment with epcoritamab. National Heart, Lung, and Blood Institute (NHLBI) investigators are experienced in testing samples treated with bsAb2,3 including epcoritamab in an ongoing pre-clinical collaboration with Genmab. Addressing the objectives of this correlative study will advance the science and clinical application of epcoritamab specifically as well as T-cell engaging bsAb in general as an emerging class of immunotherapy for cancer. The study is enrolling by invitation only.
Detailed description
Study Description: Subjects enrolled in GCT3013-03, a phase 1b/2 study of epcoritamab in R/R CLL and RS, at the National Institutes of Health (NIH) Clinical Center (CC) will be invited to simultaneously participate in this companion correlative study. Subjects will undergo percutaneous lymph node coreneedle biopsies, bone marrow biopsies, lymphapheresis, and blood draws for pharmacodynamic evaluation of tumor and immune cells in affected tissue sites and blood before and during treatment with epcoritamab. Objectives: Primary Objective: -Assess the pharmacodynamic effects of epcoritamab in the tumor microenvironment. Secondary Objectives: * Assess the pharmacodynamic effects of epcoritamab in blood * Investigate clonal dynamics during treatment with epcoritamab Exploratory Objective: -Evaluate pharmacodynamic and predictive biomarkers Endpoints: Primary Endpoint: -Immunophenotype and transcriptome of T cells and tumor cells in lymph node and bone marrow Secondary Endpoints: * Immunophenotype and transcriptome of T cells and tumor cells in peripheral blood * DNA sequencing of tumor cells Exploratory Endpoints: -Tests include, but are not limited to single cell multiomics, bulk lymph node transcriptome cytokine analysis
Interventions
DRUGepcoritamab
Samples from subjects receiving epcoritamab on another clinical trial GCT3013-03 will be collected.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Must be undergoing screening for GCT3013-03 * Stated willingness to comply with all study procedures and availability for the duration of the study * Ability of subject to understand and the willingness to sign a written informed consent document.
Exclusion criteria
None
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immunophenotype and transcriptome of T cells and tumor cells in lymph node and bone marrow | 25 days (Cycle 1 Day 25) |
Secondary
| Measure | Time frame |
|---|---|
| Immunophenotype and transcriptome of T cells and tumor cells in peripheral blood | 167 Days (Cycle 7 Day 1) |
| DNA sequencing of tumor cells | 167 Days (Cycle 7 Day 1) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAdrian U Wiestner, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Outcome results
None listed