Hypoxia-Specific Imaging to Predict Outcomes of Chimeric Antigen Receptor T-cell Therapy

Pilot Study of Hypoxia-Specific Imaging to Predict Outcomes of Chimeric Antigen Receptor T-Cell Therapy

This study evaluates whether tumors present in patients with cancer who are planned to get CAR T-cells have low amounts of oxygen (hypoxia). PET scans may be used to check the amounts of oxygen within areas of cancer with a special radioactive tracer called FAZA that specifically looks for areas of low oxygen. This study is being done to help researchers determine how the amount of oxygen within areas of cancer affect how well CAR T-cells kill cancer cells.

Study Overview

• Status: Completed
• Conditions: Refractory Plasma Cell Myeloma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Malignant Neoplasm; Refractory Malignant Neoplasm; Recurrent High Grade B-Cell Lymphoma; Refractory High Grade B-Cell Lymphoma; Recurrent Aggressive Non-Hodgkin Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Aggressive Non-Hodgkin Lymphoma
• Intervention / Treatment: Procedure: Positron Emission Tomography; Drug: Fluorine F 18-fluoroazomycin Arabinoside

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the incidence of intratumoral hypoxia in patients with relapsed or refractory (R/R) malignancies before treatment with chimeric antigen receptor (CAR) T-cell therapy.

SECONDARY OBJECTIVE:

I. To evaluate the association between intratumoral hypoxia and clinical responses to CAR T-cell therapy.

EXPLORATORY OBJECTIVES:

I. To correlate intratumoral hypoxia with markers of CAR T-cell activity and toxicity.

2. To correlate pre-therapy fluorine F 18-fluoroazomycin arabinoside (18F-FAZA) uptake with pre-therapy 18Ffluorodeoxyglucose (FDG) positron emission tomography (PET) uptake (if available).

OUTLINE:

Prior to CAR T-cell therapy, patients receive 18F-FAZA intravenously (IV). Beginning 2 hours after injection, patients undergo a single PET scan. Patients are followed for up to 6 months after CAR T-cell therapy.

• Study Type: Observational
• Enrollment (Actual): 23

Contacts and Locations

• Study Contact: Name: Morgan Tate; Phone Number: 877-827-3222; Email: Morgan.Tate@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with relapsed or refractory malignancies who are planning to receive CAR T-cell therapy at University of California, San Francisco (UCSF)

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of:

  • Aggressive lymphoma, including: Diffuse large B-cell lymphoma (DLBCL) (including transformed disease), high-grade B-cell lymphoma, or primary mediastinal B-cell lymphoma
  • Multiple myeloma (MM), with imaging within 6 months of enrollment demonstrating >= 1 plasmacytoma measuring >= 5 cm along any axis
  • Other malignancy with radiographically measurable disease
• R/R disease with planned receipt of CAR T-cell therapy at University of California, San Francisco (UCSF), either through an Food and Drug Administration-approved CAR construct or through a separate interventional clinical trial
• Ability to provide informed consent prior to study entry

Exclusion Criteria:

• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with participant's safety, provision of informed consent, or compliance with study procedures
• Pregnancy or active lactation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Diagnostic (18F-FAZA PET scan); Prior to CAR T-cell therapy, patients receive administration of 18F-FAZA IV. Patients will then undergo a vertex-thigh PET scan approximately 2 hours after injection of 18FFAZA lasting 30-45 minutes.

Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Drug: Fluorine F 18-fluoroazomycin Arabinoside; Given IV; Other Names: 18F-FAZA; 18F-Fluoroazomycin Arabinoside; FAZA F-18; Fluoroazomycin Arabinoside F-18

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of fluorine F 18-fluoroazomycin arabinoside (18F-FAZA) positron emission tomography (PET) scans with positive hypoxic volume (HV)	Will calculate the uniformly minimum-variance unbiased estimator, p-value and 95% confidence interval (CI) for the response rates.	After completion of one-time 18F-FAZA PET scan, 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response (OR)	Will determine OR at any time point as attainment of either complete response (CR) or partial response (PR). Logistic regressions will be used to evaluate the association between OR and intratumoral hypoxia, where hypoxia is analyzed as a binary and a continuous covariate.	At 30, 90, and 180 days after chimeric antigen receptor (CAR) T-cell therapy, up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Serum Ferritin levels	Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.	Up to 6 months after CAR T-cell therapy
Change in Mean C-reactive protein (CRP) levels	Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.	Up to 6 months after CAR T-cell therapy
Change in Mean Fibrinogen Levels	Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.	Up to 6 months after CAR T-cell therapy
Change in Hepatic aminotransferase Levels	Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.	Up to 6 months after CAR T-cell therapy
Incidence of cytokine release syndrome (CRS), neurotoxicity, or other adverse events (AEs) attributed to CAR T-cell therapy	Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.	Up to 6 months after CAR T-cell therapy
Standardized uptake value maximum (SUVmax) calculations for tumor sites based on 18F-FAZA versus fludeoxyglucose F-18 (18F-FDG) uptake	Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.	Up to 6 months after CAR T-cell therapy

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: C. Babis Andreadis, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2020
• Primary Completion (Actual): August 9, 2023
• Study Completion (Actual): August 9, 2023

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Signs and Symptoms, Respiratory; Aggression; Neoplasms; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence; Lymphoma, Non-Hodgkin; Hypoxia; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluoroazomycin arabinoside
• Other Study ID Numbers: 20921; NCI-2020-03216 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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
• product manufactured in and exported from the U.S.: No