Study to Evaluate CD8 PET Imaging as a Marker of Immune Response to Stereotactic Body Radiation Therapy (ELIXR)

NCT05371132 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 21221NCI-2022-02037P30CA033572
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

"This phase I trial investigates the effect of radiation therapy on the immune system, specifically CD8 positive (+) T cells, in lymphoma patients receiving bridging radiation therapy before CAR T-cell infusion, and metastatic patients with solid tumor malignancies receiving SBRT. CD8+ T cells are mainly found in lymph tissue and play a significant role in anti-tumor immunity. These cells can infiltrate tumor cells and kill them. Radiation therapy may recruit CD8 T cells and this recruitment may help with tumor control. Diagnostic procedures, such as zirconium Zr 89-Df-crefmirlimab positron emission tomography (PET), may be a less invasive way to check and monitor for CD8+ T cells before and after radiation therapy."

Conditions

Lymphoma; Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Change in CD8 positron emission tomography (PET) maximum standardized uptake value (SUVmax)

  CD8 PET SUV will be measured as SUVmax, the maximum SUV measurement within the tumor voxels. If patients have multiple tumors treated with stereotactic body radiation therapy (SBRT), average within-tumor change will be used for that patient for the primary analysis. As a result, this primary analysis is a comparison of the change in CD8 PET SUV in 10 patients.

  Pre-SBRT to post-SBRT (comparison of CD8 PET SUV at day -1, and at 1 week after completion of SBRT)

Secondary Outcomes (6)

• Time evolution of CD8 PET SUV (decay corrected)

  From pre-SBRT to post-SBRT (comparison of CD8 PET SUV at day -1, and at each of 5 fractions of SBRT administered 2-5 days apart, and additional imaging 1-2 weeks after completion of SBRT)

• Site specific differences in immune characterization (CD8 PET SUV) and changes

  From pre-SBRT to post-SBRT ( CD8 PET SUV at day -1, and at each of 5 fractions of SBRT administered 2-5 days apart, and additional imaging 1-2 weeks after completion of SBRT).

• Histology specific differences in immune characterization (CD8 PET SUV) and changes

  From pre-SBRT to post-SBRT ( CD8 PET SUV at day -1, and at each of 5 fractions of SBRT administered 2-5 days apart, and additional imaging 1-2 weeks after completion of SBRT).

• Evaluation of tumor response (fludeoxyglucose F-18 [FDG] PET and/or computed tomography [CT]) as it relates to both baseline CD8 PET SUV and changes observed after SBRT.

  Pre-SBRT to post-SBRT (1-2 weeks after completion of SBRT). Additional RECIST response assessments will be conducted per standard of care and will be assessed for up to 2 years to compare to CD8 SUVs post-SBRT and changes in CD8 SUVs.

• CD8 PET SUV (Subset)

  Pre-bridging radiation to post-CAR T cell therapy (approximately at least 7 days after CAR T cell infusion). Additional response and survival data will be collected up to 2 years after completion of study therapy.

Other Outcomes (1)

• Correlation between immune characterization of blood samples and CD8 PET SUVs and tumor response

  Pre-SBRT to post-SBRT (1 week after completion of SBRT)

Study Arms (1)

Basic science (zirconium Zr 89-Df-crefmirlimab, PET, SBRT)

EXPERIMENTAL

Patients receive zirconium Zr 89-Df-crefmirlimab IV over 5-10 minutes and then under PET imaging 24 hours after infusion before and after SBRT. Patients undergo SBRT every 2-5 days for a total of 5 fractions. For lymphoma patients only, IMRT on consecutive days may be used.

Procedure: Positron Emission Tomography; Radiation: Stereotactic Body Radiation Therapy; Drug: Zirconium Zr 89-Df-Crefmirlimab; Radiation: Intensity Modulated Radiation Therapy

Interventions

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Basic science (zirconium Zr 89-Df-crefmirlimab, PET, SBRT)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Basic science (zirconium Zr 89-Df-crefmirlimab, PET, SBRT)

Zirconium Zr 89-Df-Crefmirlimab DRUG

Given IV

Also known as: 89Zr-Crefmirlimab Berdoxam, 89Zr-Desferrioxamine-IAB22M2C, 89Zr-Df-Crefmirlimab, 89Zr-Df-IAB22M2C, Zirconium Zr 89-Df-IAB22M2C, ZIRCONIUM ZR-89-DESFERRIOXAMINE-IAB22M2C

Basic science (zirconium Zr 89-Df-crefmirlimab, PET, SBRT)

Intensity Modulated Radiation Therapy RADIATION

IMRT for Lymphoma patients only

Also known as: IMRT

Basic science (zirconium Zr 89-Df-crefmirlimab, PET, SBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Participant is willing and able to comply with all protocol required procedures
• Age: \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Metastatic patients of any solid tumor malignancy amenable for SBRT as determined by the radiation oncologist
• Lymphoma patients may be allowed as determined by the principal investigator (PI)
• No change in systemic treatment regimen for past 2 months prior to start of SBRT
• Patients able to comply with daily PET after SBRT
• Patient meets all clinical safety lab values per institution's standard of care, or Investigator's discretion, for patients receiving cancer treatment
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
• If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential to use effective double barrier contraceptive methods or abstain from heterosexual activity for the course of the study through at least 30 days after the last administration of the CD8 PET tracer
• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

You may not qualify if:

• Patient who have splenic disorders or had splenectomy that per PI would interfere with CD8 imaging
• Patients should not have any uncontrolled illness including ongoing or active infection
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CD8 PET tracer
• Serious nonmalignant disease or conditions that could compromise protocol objectives, in the opinion of the investigator
• Females only: Pregnant or breastfeeding
• Pregnant women are excluded from this study because CD8 PET tracer is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CD8 PET tracer, breastfeeding should be discontinued if the mother is treated with CD8 PET tracer
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Lymphoma

Interventions

Magnetic Resonance Spectroscopy; Radiosurgery; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted

Study Officials

• Savita V Dandapani

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: May 12, 2022
• Study Start: June 20, 2022
• Primary Completion (Estimated): October 5, 2026
• Study Completion (Estimated): October 5, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (1)