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

Recurrent Plasma Cell Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04409314
• Other study ID #: 20921
• Secondary ID: NCI-2020-03216
• Status: Completed
• Start date: April 16, 2020
• Est. completion date: August 9, 2023

Study information

• Verified date: August 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 9, 2023
• Est. primary completion date: August 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aggression
• Hypoxia
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms
• Neoplasms, Plasma Cell
• Recurrence
• Recurrent Aggressive Non-Hodgkin Lymphoma
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent High Grade B-Cell Lymphoma
• Recurrent Malignant Neoplasm
• Recurrent Plasma Cell Myeloma
• Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
• Refractory Aggressive Non-Hodgkin Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory High Grade B-Cell Lymphoma
• Refractory Malignant Neoplasm
• Refractory Plasma Cell Myeloma
• Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma

Intervention

Drug:
• Fluorine F 18-fluoroazomycin Arabinoside
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET scan

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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