Pilot Prospective Study for PET-CT Imaging in Participants With Relapsed/Refractory Acute Leukemias

Background

Acute lymphoblastic leukemia (ALL) accounts for about 25 percent of childhood cancers and for about 20 percent of adult leukemias. The disease can be treated with CAR T-cell infusion but non-central nervous system (CNS) extramedullary disease (EMD) is associated with lower rates of complete remission. 18-fludeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has been shown to be effective for detection of non-CNS EMD in ALL. Pre and post CAR T-cell infusion may help to predict outcomes and risk of early progression.

Objectives

To describe the number of adults with relapsed/refractory B-cell ALL who proceed to CAR T-cell therapy.

Eligibility

Participants >=18 years with relapsed/refractory B-cell ALL who are being screened for CAR T-cell clinical trial enrollment, and

Participants <18 with relapsed/refractory B cell ALL who are being screened for CAR T-cell clinical trial enrollment and have a clinical indication for FDG PET-CT prior to CAR infusion.

Design

Pilot study to add screening FDG PET-CT as part of the pre-CAR T-cell baseline evaluation with additional imaging at day 28 and future timepoints pending evidence of non-CNS EMD on initial scan....

Study Overview

• Status: Completed
• Conditions: Acute Lymphoblastic Leukemia; Relapsed/Refractory; B Cell

Detailed Description

Background

• Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, accounting for approximately 25 percent of all childhood cancer. ALL also spans the age spectrum and represents approximately 20 percent of adult leukemias.
• Despite improved survival rates for pediatric, adolescent, and adult ALL, relapse following upfront therapy is common. The recent introduction of chimeric antigen receptor (CAR) T-cell therapies has improved outcomes compared to other available salvage regimens, but limitations to its efficacy exist.
• The presence of non-central nervous system (CNS) extramedullary disease (EMD) at the time of CAR T-cell infusion is associated with lower complete remission (CR) rates compared to isolated medullary disease even with evidence of CAR trafficking to EMD sites. Despite implications for CAR therapy, the true incidence of non-CNS EMD for patients proceeding to CAR is unknown. Our retrospective study estimates the EMD rate to be as high as 21 percent.
• Although 18-fludeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) is feasible and has been shown to be high yield for detection of non-CNS EMD in ALL, it is not part of standard evaluation pre-CAR T-cell therapy.
• Recent studies examining the use of pre and post-infusion FDG PET-CT in patients with large cell lymphoma treated with CAR have shown Deauville response criteria, total metabolic tumor volume, and change of standardized uptake values (SUV) to be predictive of CAR T outcomes and risk of early progression. In addition to the use of PET-CT in monitoring CAR T response, circulating tumor DNA (ctDNA) has been shown risk stratify and predict outcomes in large cell lymphoma and can be detected prior to radiographic evidence of relapse.

Objectives

-Describe the proportion of non-CNS EMD in adult participants with relapsed/refractory BALL proceeding to CAR T-cell therapy

Eligibility

• Participants >=18 years with relapsed/refractory B cell ALL who are being screened for CAR T-cell clinical trial enrollment, and
• Participants <18 with relapsed/refractory B cell ALL who are being screened for CAR T-cell clinical trial enrollment and have a clinical indication for FDG PET-CT prior to CAR infusion.

Design

-Pilot study to add screening FDG PET-CT as part of the pre-CAR T-cell baseline evaluation with additional imaging at day 28 and future timepoints pending evidence of non-CNS EMD on initial scan.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Primary care clinic

Description

• INCLUSION CRITERIA:
• Diagnosis: Participants must have a B cell ALL (inclusive of CML with ALL transformation)

• Age: 5-39 years

  • All participants >=18 years old with relapsed/refractory B cell ALL potentially proceeding to CAR therapy at the NIH, or

  • Any participant <18 potentially proceeding to CAR therapy at the NIH with a clinical indication for FDG PET-CT prior to CAR infusion:

    • History of prior EMD
    • History of post-HSCT relapse
    • Clinical signs or incidental findings suspicious for EMD
    • Peripheral disease out of proportion of bone marrow disease burden
• Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding within 24 hours of any PET-CT scan
• Ability and willingness of participant or Legally Authorized Representative (LAR) to co-enroll on protocol 10-C-0086 "Comprehensive Omics Analysis of Pediatric Solid Tumors and Establishment of a Repository for Related Biological Studies".
• Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

• Pregnant individuals are excluded from this study
• History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study (e.g., FDG injection)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Adult; Participants >/=18 years old with relapsed/refractory B cell ALL proceeding to CAR therapy at the NIH
Pediatric; Participants <18 proceeding to CAR therapy at the NIH with a clinical indication for FDG PET-CT prior to CAR infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of non-CNS EMD in adult participants with relapsed/refractory B-ALL proceeding to CAR T-cell therapy	Estimate the fraction of adult participants who are PET positive for non-CNS EMD	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine proportion of non-CNS EMD with concurrent CNS disease or history of CNS disease	Incidence of concurrent CNS disease with non-CNS EMD.	At time of LP
Identify risk factors associated with presence of non-CNS EMD pre-CAR	Risk factors associated with presence of non-CNS EMD	through 3 months post CAR T

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nirali N Shah, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2023
• Primary Completion (Actual): December 1, 2025
• Study Completion (Actual): December 1, 2025

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: April 16, 2026

More Information

Terms related to this study

• Keywords: Imaging; Natural History; ACUTE LEUKEMIA
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 10001620; 001620-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing will be shared with subscribers to dbGAP.
• IPD Sharing Time Frame: Clinical data will be made available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• IPD Sharing Access Criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No