Imaging Apoptosis for Lymphoma Treatment Response

May 29, 2024 updated by: Washington University School of Medicine
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria (Healthy Volunteers):

  • Adult 18 years of age or older
  • No known hematological disorders
  • Considered healthy based on assessment by Principal Investigator (PI).
  • Able to provide informed consent
  • Able to comprehend and willing to follow instructions for study procedures as called for by the protocol.
  • Capable of lying still and supine within the PET/CT scanner for up to 1 hour at a time.

Exclusion Criteria (Healthy Volunteers):

  • No illicit drug use or other inhaled drug use (including pharmacologic agents, recreational agents or illicit drugs) within the past year per self-reporting mechanisms.
  • No history of claustrophobia or other preventing condition that has previously or would interfere with completion of protocol specified imaging sessions.
  • Not currently pregnant or nursing: Subject must be surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, OR of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of 18 F-FAT) is negative

Inclusion Criteria (Participants with Diffuse Large B Cell Lymphoma):

  • Men or women 18 years of age or older with a new diagnosis of lymphoma who will be treated with standard of care therapy for curative intent and at least one measurable (RECIST 1.1), FDG-avid lesion. OR recurrent DLBLC with at least one measurable (RECIST 1.1) FDA-avid lesion and a minimum of 12 months since last receiving treatment.
  • If applicable at least one FDG avid lesion accessible for biopsy (ultrasound guided preferred)
  • Able to provide informed consent
  • Able to tolerate standard of care systemic therapy as recommended by referring physician(s).

Exclusion Criteria (Participants with Diffuse Large B Cell Lymphoma):

  • Not currently pregnant or nursing: Subject must be surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, OR of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of 18 F-FAT) is negative
  • Not currently enrolled in another study using an investigational drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 = Healthy Volunteers
  • 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
Drug: 18F-FluorApoTrace
-The dose of 18F-FluorApoTrace to be given is 5 mCi
Other Names:
  • 18F-FAT
Experimental: Cohort 2a: Newly Diagnosed DLBCL patients being treated with R-CHOP
-N= 6 : 18F-FAT imaging session at baseline and Day 2-4 following Cycle 1 standard of care therapy.
Drug: 18F-FluorApoTrace
-The dose of 18F-FluorApoTrace to be given is 5 mCi
Other Names:
  • 18F-FAT
Experimental: Cohort 2b: Newly Diagnosed DLBCL patients being treated with R-CHOP
-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)
Drug: 18F-FluorApoTrace
-The dose of 18F-FluorApoTrace to be given is 5 mCi
Other Names:
  • 18F-FAT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Whole body effective dose (in rems) of a 5 mCi injection of 18F-FAT (Cohort 1 only)
Time Frame: 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.
Day 1
Radiation doses (rems) to critical organs (Cohort 1 only)
Time Frame: 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.
Day 1
Change in mean standard uptake value (SUV) (Cohort 2 only)
Time Frame: 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
Through completion of early interim treatment monitoring scan (estimated to be 14 days)
Change in maximum standard uptake value (SUV) (Cohort 2 only)
Time Frame: 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
Through completion of early interim treatment monitoring scan (estimated to be 14 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Distribution volume ratio (DVR) (Cohort 2 only)
Time Frame: 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.
Through completion of early interim treatment monitoring scan (estimated to be 14 days)
Change in percent positive caspase-3 staining (Cohort 2 only)
Time Frame: 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).
Baseline and post-treatment (estimated to be 14 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

AbbVie

Investigators

  • Principal Investigator: Farrokh Dehdashti, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 6, 2021

Primary Completion (Actual)

February 10, 2024

Study Completion (Actual)

February 10, 2024

Study Registration Dates

First Submitted

September 8, 2021

First Submitted That Met QC Criteria

September 8, 2021

First Posted (Actual)

September 17, 2021

Study Record Updates

Last Update Posted (Actual)

May 30, 2024

Last Update Submitted That Met QC Criteria

May 29, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202108112

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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