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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia; B-All
• Intervention / Treatment: Diagnostic test: NGS testing

Detailed Description

Background:

• Given the dismal outcomes for patients who experience a relapse following CD19 CART and the potential for using Hematopoietic cell transplantation (HCT) for post-CART remission consolidation for relapse prevention, there is a clear opportunity to improve outcomes for patients with B-ALL who proceed to CART. With a goal of improving overall survival, it remains critically important to be able to predict which patients are at high risk of relapse in whom an HCT would be indicated for remission consolidation. Distinguishing this high-risk cohort from low-risk patients who are able to maintain durable remission following CART and in whom HCT-associated toxicities could be avoided is equally important.
• Thus, in the context of this biomarker-based study, we propose a systematic approach utilizing the best-known biomarkers for remission monitoring which assess both functional CART persistence and incorporates antigen immunophenotype agnostic approach for disease detection will improve LFS post CD19 CART.

Objective:

-To assess efficacy of a novel biomarker-guided risk-based strategy to monitor remission, both by assessing functional CART persistence and incorporating antigen immunophenotype agnostic approach (NGS monitoring) for disease detection, to inform decisions regarding post-CART HCT needed intervention, and to successfully collect biomarker samples at the scheduled times in enrolled HCT naive B-ALL participants receiving CD19 CART.

Eligibility:

• Age >=1 year and <= 25 years old at the time of CD19 CART infusion
• Diagnosis of CD19+ B-ALL in a bone marrow morphologic complete remission and are flow cytometry measurable residual disease (MRD) negative within 42 days post CD19 CART infusion.
• Must have an allogeneic HCT donor identified for potential HCT
• B-cell aplasia post CD19 CART persisting until the time of the first on-study intervention

Design:

-This single-arm multicenter study will enroll pediatric and young adult participants to evaluate the feasibility, and potential efficacy, of a risk-based, biomarker-driven, consolidation HCT strategy following CD19 CART.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nirali N Shah, M.D.; Phone Number: (240) 760-6970; Email: shahnn@mail.nih.gov
• Study Contact Backup: Name: NCI Ped LeukemiaLymph Cell Tx Tm; Phone Number: (240) 760-6970; Email: ncilltct@mail.nih.gov

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital of Los Angeles
      • Contact: Emily Hsieh, M.D.; Phone Number: Not Listed; Email: ehsieh@chla.usc.edu
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Children's National Medical Center
      • Contact: Anant Vatsayan, M.D.; Phone Number: 202-476-2051; Email: avatsayan@childrensnational.org
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Not yet recruiting
      • Children's Healthcare of Atlanta
      • Contact: Allie Suessman; Phone Number: 404-712-4822; Email: asuessm@emory.edu
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office; Phone Number: 888-624-1937
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Dana-Farber/Boston Children s Hospital
      • Contact: Mona Li; Phone Number: 617-632-5727; Email: mona_li@dfci.harvard.edu
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute, University of Utah
      • Contact: Michael Pulsipher, M.D.; Phone Number: 801-662-4700; Email: michael.pulsipher@hci.utah.edu
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Research Center
      • Contact: Cindy Hirano; Phone Number: Not Listed; Email: chirano@fredhutch.org
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's, University of Washington
      • Contact: Corine Summers, M.D.; Phone Number: Not Listed; Email: corinnes@uw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:
• 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).

EXCLUSION CRITERIA:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1/Intervention; Systematic, frequent monitoring intervention to risk stratify pts for risk of relapse postCART	Diagnostic test: NGS testing; antigen immunophenotype agnostic approach for disease detection using blood and bone marrow samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to relapse	Defined as time from CART cell infusion to relapse	baseline to 1 year post CD19 CART infusion
Time to HCT	Defined as time from CART cell infusion to receiving HCT	baseline to 1 year post CD19 CART infusion
Leukemia Free Survival	Defined as time from CART cell infusion to first occurrence of relapse or death	baseline to 1 year post CD19 CART infusion
Overall survival	Defined as time from CART cell infusion to death	baseline to 1 year post CD19 CART infusion

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 (Estimated): June 28, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 16, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 18, 2022

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: August 11, 2025

More Information

Terms related to this study

• Keywords: B-All; Car-Cure; Result Monitoring
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 10000792; 000792-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 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.
• 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
• product manufactured in and exported from the U.S.: No