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

Completed

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

• Registration Number: NCT04409314
• Lead Sponsor: University of California, San Francisco

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.

Study Timeline

• Study Start: 2020-04-16
• Study First Submitted: 2020-05-26
• Study First Submitted QC: 2020-05-26
• Study First Posted: 2020-06-01
• Status Verified: 2023-08
• Primary Completion: 2023-08-09
• Study Completion: 2023-08-09
• Last Update Submitted: 2023-08-17
• Last Update Posted: 2023-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Diagnostic (18F-FAZA PET scan)	Positron Emission Tomography	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.
Diagnostic (18F-FAZA PET scan)	Fluorine F 18-fluoroazomycin Arabinoside	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (1)

University of California, San Francisco; 🇺🇸 San Francisco, California, United States