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...
- Conditions
- Acute Lymphoblastic LeukemiaB-All
- Interventions
- Diagnostic Test: NGS testing
- Registration Number
- NCT05621291
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1/Intervention NGS testing Systematic, frequent monitoring intervention to risk stratify pts for risk of relapse postCART
- Primary Outcome Measures
Name Time Method Efficacy of novel biomarker-guided risk based strategy to monitor remission baseline to 1 year post CD19 CART infusion NGS MRD testing of blood and bone marrow samples and evaluation of BCA
- Secondary Outcome Measures
Name Time Method Leukemia Free Survival baseline to 1 year post CD19 CART infusion Defined as time from CART cell infusion to first occurrence of relapse or death
Time to HCT baseline to 1 year post CD19 CART infusion Defined as time from CART cell infusion to receiving HCT
Time to relapse baseline to 1 year post CD19 CART infusion Defined as time from CART cell infusion to relapse
Overall survival baseline to 1 year post CD19 CART infusion Defined as time from CART cell infusion to death
Trial Locations
- Locations (8)
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
Dana-Farber/Boston Children s Hospital
🇺🇸Boston, Massachusetts, United States
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Seattle Children's, University of Washington
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States