A Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymphoblastic Leu...
A Pilot Trial to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following CAR T-cell Induced Remission in Pediatric Patients With B Lineage Acute Lymphoblastic Leukemia
2 other identifiers
interventional
60
1 country
8
Brief Summary
Background: Chimeric antigen receptor T-cell (CART) therapy is a form of immunotherapy which can be used to treat people with relapsed B-ALL. For those who achieve remission after CART alone, it may cure up to 50% of people who receive this therapy. However, for people who relapse after CART, it can be hard to achieve remission again. In patients where CART fails, stem cell transplant (HCT) can be used to prevent relapse and achieve cure. But HCT can cause serious side effects. Better testing is needed to distinguish people who can be cured with CART alone from people who may also need to have HCT. Objective: To see if the use of a series of blood and bone marrow tests at regular intervals can help monitor for B-ALL relapse after CART therapy. Eligibility: People aged 1 to 25 years with B-ALL who have had CART therapy within the past 42 days. They must never have had a blood stem cell transplant; they must also have no measurable blood cancer cells. Design: Participants will visit the clinic every 2 weeks starting 42 days after they receive CART therapy. Each visit will be about the same amount of time as a regular clinic visit. about 8 hours. Participants will have blood drawn for testing on each visit. Bone marrow biopsy/aspirate will be done during 4 of the visits at routine timepoints after CART. A needle will be inserted to draw a sample of tissue from inside the bone in the hip. A small amount of blood and tissue will be tested with ClonoSEQ and to evaluate for normal B-cells side by side with the standard tests. The combined testing may help determine whether participants are eligible for HCT and/or at risk of relapse after CART. Participants will be in the study for 2 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started May 2026
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 16, 2022
CompletedFirst Posted
Study publicly available on registry
November 18, 2022
CompletedStudy Start
First participant enrolled
May 11, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
Study Completion
Last participant's last visit for all outcomes
December 31, 2027
May 6, 2026
August 11, 2025
8 months
November 16, 2022
May 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Efficacy of novel biomarker-guided risk based strategy to monitor remission
NGS MRD testing of blood and bone marrow samples and evaluation of BCA
baseline to 1 year post CD19 CART infusion
Secondary Outcomes (4)
Time to relapse
baseline to 1 year post CD19 CART infusion
Time to HCT
baseline to 1 year post CD19 CART infusion
Leukemia Free Survival
baseline to 1 year post CD19 CART infusion
Overall survival
baseline to 1 year post CD19 CART infusion
Study Arms (1)
1/Intervention
EXPERIMENTALSystematic, frequent monitoring intervention to risk stratify pts for risk of relapse postCART
Interventions
antigen immunophenotype agnostic approach for disease detection using blood and bone marrow samples
Eligibility Criteria
You may qualify if:
- Age \>=1 year and \<= 25 years old at the time of CD19 CART infusion
- Confirmed diagnosis of CD19+ B-ALL with an informative NGS clonality sample
- Have an informative NGS clonality sample for MRD assessment based on immunoglobulin rearrangement in bone marrow or blood at any time of active disease between diagnosis and CD19 CART infusion and any time prior to the first on-study intervention confirmed by NGS MRD testing.
- Post-CD19 CART infusion disease status:
- Are in bone marrow morphologic complete remission and are flow cytometry measurable residual disease (MRD) negative within 42 days post CD19 CART infusion.
- Are NGS MRD negative by tracking sample in the bone marrow within 42 days post CD19 CART infusion confirmed by NGS MRD testing.
- Received first CD19 (4-1BB) CART within 42 days prior to enrollment. Note: Eligible CART including FDA approved Kymriah (tisagenlecleucel) infused on a treatment plan, research study, or other comparable 4-1BB based constructs.
- Study chairs will determine whether other 4-1BB CART are considered comparable.
- All participants must have an allogeneic HCT donor identified for potential HCT. Note: Donor identification and selection will be according to institutional practice.
- Have B-cell aplasia (BCA) post CD19 CART persisting within 42 days post CD19 CART infusion. Note: BCA persisting is defined as \<1% B cells lymphocytes or \<50 B cells/microliter in the peripheral blood
- Performance of all screening tests prior to day 42 post CD19 CART.
- The ability of participant or parent/guardian to understand and the willingness to sign a written consent document or participants unable to consent if they are represented by a Legally Authorized Representative (LAR).
You may not qualify if:
- Prior hematopoietic stem cell transplantation (HCT)
- Recent history of the extramedullary disease (EMD) that requires ongoing radiographic surveillance (e.g., participants with active EMD at CD19 CART infusion that requires monitoring by imaging without the ability to more precisely assess disease status will be ineligible). A remote history of EMD does not exclude the participant.
- Active and/or residual central nervous system (CNS) disease that requires ongoing therapy or monitoring.
- Co-morbidities precluding myeloablative HCT. Note: Determination of co-morbidities precluding myeloablative HCT will be made by the treating transplant (HCT) physician and documented in the research record. This does not require that the participant is immediately fully eligible for HCT, only that there are no long-term comorbidities that would preclude a myeloablative approach (e.g., renal failure, severe cardiac failure, long-term oxygen requirement).
- Uncontrolled, symptomatic, intercurrent illness or social situations that would limit compliance with study requirements. Note: Determination of uncontrolled, symptomatic illness or social situation that would limit compliance with the study requirements will be made by the site-PI and documented in the research record.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
Children's Hospital of Los Angeles
Los Angeles, California, 90027, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30329, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Dana-Farber/Boston Children s Hospital
Boston, Massachusetts, 02115, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112, United States
Seattle Children's, University of Washington
Seattle, Washington, 98105, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nirali N Shah, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 16, 2022
First Posted
November 18, 2022
Study Start (Estimated)
May 11, 2026
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2027
Last Updated
May 6, 2026
Record last verified: 2025-08-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data will be made available within 10 years after completion of the primary endpoint. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
- 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.
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.