Patients with relapsed/refractory LBCL after 2 prior lines of therapy and qualify for CD19-directed CAR T-cell therapy. Eligibility for CAR T-cell therapy is based on the criteria posed by the Dutch Immune Effector Cell working group tumor board.
Conditions
Interventions
Product Name: 89Zr-CED88004
Pharmaceutical Form: Solution for injection
INN or Proposed INN: 89ZR-CED88004
Other descriptive name: 89ZR-CED88004
Concentration unit: MBq megabecquerel(s)
Concentration
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with histologically confirmed LBCL and subtypes according to the WHO 2016 criteria 2. Tumor lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures. 3. Measurable disease, as defined by Lugano criteria. 4. Signed informed consent. 5. Age =18 at the time of signing informed consent. 6. Life expectancy =12 weeks. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 8. Ability to comply with the protocol. 9. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate [=65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: 1. Signs or symptoms of infection within 2 weeks prior to ZED88082A/CED88004S injection. 2. Prior immune checkpoint inhibitor bi-specific antibody, including but not limited to anti-PD1 and anti- PD-L1 therapeutic antibodies. 3. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. 4. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ZED88082A/CED88004S, or that may affect the interpretation of the results or render the patient at high risk from complications. 5. Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective is to study the distribution of CD8+ T-cells before and after CAR T-cell therapy in the patient by ZED88082A/CED88004S-PET imaging. We will correlate the pretreatment CD8+ T-cell distribution and CD8+ CAR T-cell tumor invasion, as measured by the intensity of ZED88082A/CED88004S-PET imaging positive lesions.;Secondary Objective: • To assess heterogeneity of ZED88082A/CED88004S tumor uptake. • To correlate normal organ ZED88082A/CED88004S uptake to (serious) adverse events (possibly) related to CAR T-cell treatment. • To correlate tumor ZED88082A/CED88004S uptake with tumor and immune cell CD8-expression as assessed by a fresh contemporaneous tumor biopsy. • To correlate ZED88082A/CED88004S uptake in irradiated versus non-irradiated lymphoma lesions in patients who require radiotherapy as bridging strategy prior to CAR T-cell infusion. ;Primary end point(s): - To determine the whole-body biodistribution of the ZED88082A tracer in normal tissues and tumor lesions before and after CAR T-cell therapy. Heterogeneity of ZED88082A/CED88004S uptake evaluated by measuring standardized uptake value (SUV) on the ZED88082A/CED88004S-PET scan 2 days after ZED88082A/CED88004S injection.;Timepoint(s) of evaluation of this end point: Day -13 and +5, whereas Day 0 is day of CarT infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Correlative expression analysis between ZED88082A tracer SUV parameters in the tumor, CD8 expression in tumor biopsy, and response to CAR T-cell therapy (see 10.2.1 for efficacy measurements). - To perform correlative expression analysis between SUV parameters ZED88082A tracer in the tumor, CD8 expression in tumor biopsy, and SUV parameters the tumor and whole-body and CAR T-cell persistence, peak level and CAR T-cell phenotype as measured in the peripheral blood. Immune cell CD8 expression and tumor and immune cell PD-L1 expression analyses, as well as evaluation of other markers of lymphocytic infiltration in a tissue biopsy, will be correlated to ZED88082A tumor uptake, evaluated by measuring standardized uptake value (SUV parameters on the ZED88082A/CED88004S-PET scan 2 days after ZED88082A/CED88004S injection. Correlative expression analysis between ZED88082A tracer max in the tumor, and grade 1-5 adverse events to CAR T-cell therapy, including cytokine release syndrome and neurotoxicity. Safety assessment through summaries of adverse events, changes in laboratory test results (if evaluation is indicated), changes in vital signs, and exposure to ZED88082A/CED88004S. Adverse event data will be recorded and summarized according to NCI CTCAE v5.0. Serious adverse events, including deaths, will be listed separately and will be summarized. For events of varying severity, the highest grade will be used in summaries. Relevant laboratory tests, including circulating lymphocyte populations and vital signs (heart rate, respiratory rate, blood pressures, and temperature) data will be displayed by time, with grade 3 and 4 values identified, where appropriate. - to correlate ZED88082A/CED88004S uptake in lymphoma to infield and outfield radiation therapy in patients receiving radiation therapy that require bridging to CAR T-cell infusion. Assessment of dosimetry, by calculations of radioactivity in Bq or mSv of ZED88082A concentration in tumor targ | — |
Countries
Netherlands
Contacts
Public ContactTrial Data Center
University Medical Center Groningen
Outcome results
None listed