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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05969002
• Other study ID #: 10001620
• Secondary ID: 001620-C
• Status: Recruiting
• Start date: August 25, 2023
• Est. completion date: April 30, 2026

Study information

• Verified date: April 24, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: NCI Pediatric Leukemia, Lymphoma Transpl
• Phone: (240) 760-6970
• Email: ncilltct[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background Acute lymphoblastic leukemia (ALL) accounts for about 25% of childhood cancers and for about 20% 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.

Description:

Background - Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, accounting for approximately 25% of all childhood cancer. ALL also spans the age spectrum and represents approximately 20% 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%. - 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: April 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 39 Years

Eligibility

• 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 coenroll 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 women 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)

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• B Cell
• Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed/Refractory

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Correlation of bone marrow CAR T-cell response by flow cytometry with ctDNA	Bone marrow response by flow cytometry with ctDNA	day 28
Secondary	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
Secondary	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

External Links

•   NIH Clinical Center Detailed Web Page