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

Study Overview
=================
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.

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.

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

Conditions
-----------------
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 / Treatment
-----------------
* Drug: Fluorine F 18-fluoroazomycin Arabinoside
* Procedure: Positron Emission Tomography


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Diagnostic (18F-FAZA PET scan)<br>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<br>* Given IV<br>* Other names: Fluoroazomycin Arabinoside F-18;Procedure: Positron Emission Tomography<br>* Undergo PET scan<br>* Other names: proton magnetic resonance spectroscopic imaging;|

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 |