Imaging Apoptosis for Lymphoma Treatment Response
- Registration Number
- NCT05048732
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
Apoptosis is a specific form of cell death that leads to clearance of dead cells without causing inflammation or injury to normal adjacent tissues. Targeted cancer therapeutics that target this pathway for tumor cell death induction are in development, but few specific biomarkers of apoptosis are available to assess treatment response. Apoptosis also occurs in response to standard anthracycline or combination therapies such as rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), rituximab, etoposide, phosphate, prednisone, vincristine sulfacte, cyclophosphamide, and doxorubicin hydrocholoride (R-EPOCH) used to treat many different histopathological types of lymphoma including Hodgkin and non- Hodgkin lymphoma such as diffuse large B-cell lymphoma (DLBCL), Burkitts lymphoma, primary mediastinal B-cell lymphoma and double hit DLBCL. Caspase-3 activation occurs as a result of apoptosis and may be a specific marker of apoptosis. Therefore, this study will assess whether 18F-FluorApoTrace (18F-FAT), a caspase-3 targeted tracer, has a reasonable dosimetry profile and can be used to detect apoptosis in patients with lymphoma being treated with standard therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 12
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 = Healthy Volunteers 18F-FluorApoTrace * Healthy volunteers (N=6, three male, three female) will be recruited to undergo a single 18F-FAT PET/CT imaging session for radiation dosimetry estimates. * 18F-FAT administration followed by body imaging at 3 time points * 0-60 min = multiple quick body scans * 120 min post injection = body scan * 240 min post injection = body scan Cohort 2a: Newly Diagnosed DLBCL patients being treated with R-CHOP 18F-FluorApoTrace -N= 6 : 18F-FAT imaging session at baseline and Day 2-4 following Cycle 1 standard of care therapy. Cohort 2b: Newly Diagnosed DLBCL patients being treated with R-CHOP 18F-FluorApoTrace -N=9: 18F-FAT imaging session at baseline and best time point determined from Cohort 2a (2 days post Cycle 1 standard of care therapy)
- Primary Outcome Measures
Name Time Method Whole body effective dose (in rems) of a 5 mCi injection of 18F-FAT (Cohort 1 only) Day 1 -The time activity curves will be created using all the scans obtained and integrated to determine organ residence times. This data, plus the counts and volumes from urine collection(s) after tracer injection, will then be used to calculate the dosimetry using OLINDA/EXM v1.1. The calculated residence times will be used with the program OLINDA/EXM for 18F and using the adult human (adult female or male) model to calculate the whole body effective dose.
Change in mean standard uptake value (SUV) (Cohort 2 only) Through completion of early interim treatment monitoring scan (estimated to be 14 days) -30 minutes and 60-90 minutes post pre-treatment baseline monitoring scan and 30 minutes and 60-90 minutes post early interim treatment monitoring scan
Radiation doses (rems) to critical organs (Cohort 1 only) Day 1 The time activity curves will be created using all the scans obtained and integrated to determine organ residence times. This data, plus the counts and volumes from urine collection(s) after tracer injection, will then be used to calculate the dosimetry using OLINDA/EXM v1.1. The calculated residence times will be used with the program OLINDA/EXM for 18F and using the adult human (adult female or male) model to calculate the individual organ radiation dose.
Change in maximum standard uptake value (SUV) (Cohort 2 only) Through completion of early interim treatment monitoring scan (estimated to be 14 days) -30 minutes and 6-90 minutes post pre-treatment baseline monitoring scan and 30 minutes and 60-90 minutes post early interim treatment monitoring scan
- Secondary Outcome Measures
Name Time Method Distribution volume ratio (DVR) (Cohort 2 only) Through completion of early interim treatment monitoring scan (estimated to be 14 days) -DVR will be calculated by reference region Logan plot analysis, in the largest (by size) and most FDG-avid (by maximum SUV) lymphoma lesions.
Change in percent positive caspase-3 staining (Cohort 2 only) Baseline and post-treatment (estimated to be 14 days) * Biopsy samples from baseline and post-treatment will be collected. Immunohistochemical analysis will be performed for caspase-3 staining.
* The preference for the post-treatment biopsy is for the biopsy to be performed on the same day as 18F-FAT imaging with imaging occurring prior to biopsy (either 2 or 4 days after receiving cycle 1 of R-CHOP). However, due to scheduling conflicts biopsy performed 2-7 days after cycle 1 R-CHOP therapy will be allowed.
* The staining intensity will be assessed semi-quantitatively using a four-point scale (No Signal=0, Mild=1, Moderate=2, Strong=3). The percentage of stained cells at each intensity level will also be graded typically as 0 (\<5%), 1 (5-25%), 2 (26-50%), 3 (51-75%), and 4 (\>75%). The intensity score and percentage of positive cells will be then added to produce the final scores (0-7).
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States