Imaging Apoptosis for Lymphoma Treatment Response

NCT05048732 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: 202108112
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• Whole body effective dose (in rems) of a 5 mCi injection of 18F-FAT (Cohort 1 only)

  -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)

  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)

  -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)

  -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 Outcomes (2)

• Distribution volume ratio (DVR) (Cohort 2 only)

  Through completion of early interim treatment monitoring scan (estimated to be 14 days)

• Change in percent positive caspase-3 staining (Cohort 2 only)

  Baseline and post-treatment (estimated to be 14 days)

Study Arms (3)

Cohort 1 = Healthy Volunteers

EXPERIMENTAL

* 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

Cohort 2a: Newly Diagnosed DLBCL patients being treated with R-CHOP

EXPERIMENTAL

-N= 6 : 18F-FAT imaging session at baseline and Day 2-4 following Cycle 1 standard of care therapy.

Drug: 18F-FluorApoTrace

Cohort 2b: Newly Diagnosed DLBCL patients being treated with R-CHOP

EXPERIMENTAL

-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

Interventions

18F-FluorApoTrace DRUG

-The dose of 18F-FluorApoTrace to be given is 5 mCi

Also known as: 18F-FAT

Cohort 1 = Healthy Volunteers; Cohort 2a: Newly Diagnosed DLBCL patients being treated with R-CHOP; Cohort 2b: Newly Diagnosed DLBCL patients being treated with R-CHOP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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).
• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• AbbVie: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Farrokh Dehdashti, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 17, 2021
• Study Start: December 6, 2021
• Primary Completion: February 10, 2024
• Study Completion: February 10, 2024
• Last Updated: May 30, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)