Hypoxia-Specific Imaging to Predict Outcomes of Chimeric Antigen Receptor T-cell Therapy
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
PRIMARY OBJECTIVE:
- 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:
- To evaluate the association between intratumoral hypoxia and clinical responses to CAR T-cell therapy.
EXPLORATORY OBJECTIVES:
- To correlate intratumoral hypoxia with markers of CAR T-cell activity and toxicity.
- 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 Design
Arms and Interventions
| Arm | 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. |
Drug: Fluorine F 18-fluoroazomycin Arabinoside
Given IV
Other Names:
Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of fluorine F 18-fluoroazomycin arabinoside (18F-FAZA) positron emission tomography (PET) scans with positive hypoxic volume (HV) [After completion of one-time 18F-FAZA PET scan, 1 day]
Will calculate the uniformly minimum-variance unbiased estimator, p-value and 95% confidence interval (CI) for the response rates.
Secondary Outcome Measures
- Overall response (OR) [At 30, 90, and 180 days after chimeric antigen receptor (CAR) T-cell therapy, up to 6 months]
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.
Other Outcome Measures
- Change in Mean Serum Ferritin levels [Up to 6 months after 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.
- Change in Mean C-reactive protein (CRP) levels [Up to 6 months after 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.
- Change in Mean Fibrinogen Levels [Up to 6 months after 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.
- Change in Hepatic aminotransferase Levels [Up to 6 months after 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.
- Incidence of cytokine release syndrome (CRS), neurotoxicity, or other adverse events (AEs) attributed to CAR T-cell therapy [Up to 6 months after 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.
- Standardized uptake value maximum (SUVmax) calculations for tumor sites based on 18F-FAZA versus fludeoxyglucose F-18 (18F-FDG) uptake [Up to 6 months after 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically confirmed diagnosis of:
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Aggressive lymphoma, including: Diffuse large B-cell lymphoma (DLBCL) (including transformed disease), high-grade B-cell lymphoma, or primary mediastinal B-cell lymphoma
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Multiple myeloma (MM), with imaging within 6 months of enrollment demonstrating
= 1 plasmacytoma measuring >= 5 cm along any axis
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Other malignancy with radiographically measurable disease
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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
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Ability to provide informed consent prior to study entry
Exclusion Criteria:
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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
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Pregnancy or active lactation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Francisco | San Francisco | California | United States | 94143 |
Sponsors and Collaborators
- University of California, San Francisco
Investigators
- Principal Investigator: C. Babis Andreadis, MD, University of California, San Francisco
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20921
- NCI-2020-03216