PET-Enabled Dual-Energy CT in Multiple Myeloma

Official title

PET-enabled Dual-energy CT for Oncological Applications

Overview

This pilot study will evaluate a new imaging method called PET-enabled dual-energy CT for measuring bone and soft-tissue composition in bone marrow. The study will enroll adults with multiple myeloma who are scheduled to receive CAR T-cell therapy and healthy adult participants. All participants will undergo research imaging with dynamic 18F-FDG PET/CT and X-ray dual-energy CT. Participants with multiple myeloma will have imaging before CAR T-cell therapy and again after therapy. Healthy participants will have one imaging visit. The main goal is to compare bone and soft-tissue fraction measurements from PET-enabled dual-energy CT with measurements from standard X-ray dual-energy CT. The study will also explore whether corrected PET measurements are associated with bone marrow measurable residual disease, treatment response, and CAR T-cell therapy toxicities in participants with multiple myeloma. This study is not expected to provide direct medical benefit to participants. The information learned may help improve future PET/CT imaging methods for cancer evaluation.

Detailed description

This is a single-institution, prospective pilot study evaluating PET-enabled dual-energy CT (DECT) for quantitative bone marrow imaging. The study will enroll adults with multiple myeloma who are scheduled to receive CAR T-cell therapy and healthy adult participants for comparison.

PET-enabled DECT is an imaging method that uses data from a standard time-of-flight PET/CT scan to generate a high-energy attenuation image. This image is combined with the standard X-ray CT image to create a dual-energy image pair. The goal is to measure tissue composition, including bone fraction and soft-tissue fraction, without requiring dedicated dual-energy PET/CT hardware.

All participants will undergo research imaging with dynamic 18F-FDG PET/CT and X-ray DECT. Participants with multiple myeloma will undergo baseline imaging before CAR T-cell therapy and follow-up imaging after therapy. Healthy participants will undergo one imaging visit. Multiple myeloma participants will also have bone marrow measurable residual disease (MRD), treatment response, and CAR T-cell therapy toxicity data collected from standard clinical care or related clinical assessments.

The primary objective is to develop and validate the new DECT method for quantitatively measuring tissue compositions of bone marrow regions in multiple myeloma and healthy participants using X-ray DECT as the reference. Secondary objectives include: To determine whether bone fraction in bone marrow differs between MM patients and healthy participants and whether PET-enabled DECT can accurately estimate bone fraction for correcting PET-based bone-marrow metabolic measurements; and, to evaluate relationships between corrected PET measures and bone marrow MRD and treatment response and toxicities of CAR T-cell therapy in MM patients This study is exploratory and is designed to collect preliminary data to support future larger studies. The research imaging is not intended to guide clinical care, and participants are not expected to receive direct medical benefit from participation. The information learned may help improve quantitative PET/CT imaging methods for future cancer evaluation and treatment monitoring.

Interventions

• Diagnostic test PET-enabled dual-energy CT imaging
  18F-FDG will be administered intravenously for dynamic PET/CT imaging.
• Diagnostic test X-ray dual-energy CT imaging
  Participants will undergo X-ray dual-energy CT imaging. Measurements from X-ray dual-energy CT will be used as the reference method for comparison with PET-enabled dual-energy CT measurements.

Primary outcome measures

• Agreement between PET-enabled DECT and X-ray DECT measurements of bone marrow tissue fractions [Time frame: Baseline imaging visit; and for multiple myeloma participants, follow-up imaging at approximately Day +90 after CAR T-cell therapy initiation]

Secondary outcome measures (4)

• Difference in bone marrow bone fraction between multiple myeloma participants and healthy participants [Time frame: Baseline imaging visit]
• Corrected 18F-FDG standardized uptake value in bone marrow [Time frame: Baseline imaging visit; and for multiple myeloma participants, follow-up imaging at approximately Day +90 after CAR T-cell therapy initiation]
• Association between corrected PET measures and bone marrow measurable residual disease [Time frame: Baseline and follow-up assessments through approximately Day +90 after CAR T-cell therapy initiation]
• Association between corrected PET measures and CAR T-cell therapy response and toxicities [Time frame: Baseline imaging through approximately Day +90 after CAR T-cell therapy initiation]

Eligibility criteria

Inclusion criteria

For all research participants:

• Adults (age ≥ 18 years old)
• Ability to understand and willingness to sign an informed consent form
• Ability to adhere to the study visit schedule and other protocol requirements.
• Willing and able to fast for at least 6 hours before and for the duration of the scan
• No strenuous exercise for 24 hours prior to being scanned
• Willing to lie on the scanner bed for up to 60 minutes

For healthy volunteers only:

• Free of history of cardiovascular, inflammatory, infections or metabolic diseases that would result in changes in bone marrow.

For cancer patients only:

• Patients with multiple myeloma who are planned to receive CAR T-cell therapy with any FDA-approved product, including Idecel and Ciltacel. Patients with prior chemo-immunotherapy are permitted.
• Able to undergo bone marrow aspirate/biopsy procedure

Exclusion criteria

• Self-reported history of dysphoria or anxiety in closed spaces
• Body weight >240 kg due to limitations of the scanner bed
• Pregnant or breast-feeding (due to risks of ionizing radiation; urine pregnancy test will be administered prior to start of each PET/CT session for all participants between 18 to 60 years old who are able to get pregnant, unless documented hysterectomy or bilateral ovarian removal is available)
• Blood glucose greater than 200 as assessed by fingerstick method before injection of 18F-FDG
• Concurrent or prior enrollment in a separate research study involving a PET scan performed within the last 12 months for research purposes only. That is, PET scans are not performed as part of a patient's treatment plan (e.g. standard of care, therapeutic purposes, or clinical care) and the research study did not intend to provide therapeutic benefit to the patient.
• Prisoners
• Any condition that would prevent the understanding or rendering of informed consent.
• Any comorbidity that, in the opinion of the investigator, could compromise protocol objectives.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• UC Davis EXPLORER Molecular Imaging Center — Sacramento

Identifiers

NCT: NCT07646873 · 2399411 · 1R01EB036562-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗