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...

Launched by NATIONAL CANCER INSTITUTE (NCI) · Nov 17, 2022

Keywords

ClinConnect Summary

This clinical trial is looking at how specific blood and bone marrow tests can help doctors monitor children and young adults with B-cell Acute Lymphoblastic Leukemia (B-ALL) who have received a special treatment called CART therapy. CART therapy helps some patients reach remission, meaning their cancer is no longer detectable. However, for those who relapse, it can be challenging to achieve remission again. The study aims to find out if regular testing can help identify patients who may need a stem cell transplant to improve their chances of a cure.

To join the trial, participants must be between 1 and 25 years old, have been diagnosed with B-ALL, and have received CART therapy within the last 42 days. They should not have had a previous stem cell transplant and must have no detectable cancer cells in their blood. Participants will visit the clinic every two weeks for a year, where they will have blood drawn and possibly a bone marrow sample taken to monitor their progress. This study hopes to provide better information on managing B-ALL after CART therapy and help doctors make important treatment decisions.

Gender

ALL

Eligibility criteria

• * 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.