NGS Monitoring for Acute Lymphoblastic Leukemia

Recruiting at 8 trial locations

Overseen By Nirali N Shah, M.D.

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Prior HCT, CNS disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find better ways to monitor relapses in patients with B-ALL, a type of blood cancer, who have received CART therapy, a specialized treatment using modified immune cells. By conducting regular blood and bone marrow tests, researchers hope to identify which patients can be cured with CART alone and which might need an additional treatment called a stem cell transplant. This approach could help avoid unnecessary side effects from the transplant. Suitable participants have recently undergone CART therapy, are in remission, and have not previously had a stem cell transplant. Participants will visit the clinic every two weeks for up to two years for testing. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve future treatment strategies for B-ALL patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that this monitoring protocol is safe for patients with B-ALL?

Research has shown that next-generation sequencing (NGS) is generally safe for patients. NGS, a type of DNA test, helps doctors learn more about a person’s cancer. Studies have found that NGS can aid in planning treatment and checking for cancer recurrence. The testing itself raises no major safety concerns, as it primarily involves analyzing blood or tissue samples, which are common in medical care.

One study detected tiny amounts of remaining cancer cells in some patients using NGS testing, but more research is needed to understand the implications. Overall, NGS is well-tolerated, with no reports of serious side effects from the testing process itself. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Next-Generation Sequencing (NGS) testing for monitoring Acute Lymphoblastic Leukemia (ALL) because it offers a cutting-edge way to detect minimal residual disease with extreme sensitivity. Unlike traditional methods, such as bone marrow biopsies, NGS can analyze genetic material from a simple blood sample, making it far less invasive. This method allows for more frequent monitoring, which means doctors can catch potential relapses earlier and tailor treatments to individual patient risk levels. By providing a more precise picture of a patient's cancer status, NGS testing has the potential to significantly improve outcomes for those battling ALL.

What evidence suggests that this monitoring method is effective for detecting B-ALL relapse after CART therapy?

Research has shown that next-generation sequencing (NGS) is a promising method for monitoring minimal residual disease (MRD) in people with B-cell acute lymphoblastic leukemia (B-ALL). NGS is highly sensitive and can detect tiny amounts of cancer cells that other methods might miss. Studies have found that NGS more accurately predicts cancer recurrence and patient survival than traditional methods. This trial will incorporate NGS into a systematic, frequent monitoring intervention to stratify patients by relapse risk after CAR T-cell therapy. By using NGS, doctors aim to better identify those at risk of relapse after initial CAR T-cell therapy and those who can be safely monitored without additional treatments. ^{3 6 7 8 9}

Who Is on the Research Team?

Nirali N. Shah

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to 25 with B-ALL who have recently undergone CART therapy but haven't had a stem cell transplant. They should be in remission, without measurable cancer cells, and have an identified donor for potential future HCT.

Inclusion Criteria

My leukemia is CD19 positive according to a specific genetic test.

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 and within 14 days prior to the first on-study intervention; Are NGS MRD negative by tracking sample in the bone marrow within 42 days post CD19 CART infusion and within 14 days prior to the first on-study intervention confirmed by NGS MRD testing; Have an absolute neutrophil count (ANC) > 500 cell/mm^3 without needing growth factor support by 42 days post CD19 CART infusion and within 4 days prior to the first on-study intervention; Received first CD19 (4-1BB) CART within 42 days prior to the first on-study intervention; All participants must have an allogeneic HCT donor identified for potential HCT; Have B-cell aplasia (BCA) post CD19 CART persisting within 14 days prior to the first on-study intervention; 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)

I am between 1 and 25 years old.

Exclusion Criteria

I have had a stem cell transplant before.

Co-morbidities precluding myeloablative HCT; Determination of co-morbidities precluding myeloablative HCT will be made by the treating transplant (HCT) physician and documented in the research record

Uncontrolled, symptomatic, intercurrent illness or social situations that would limit compliance with study requirements; 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monitoring

Participants undergo systematic, frequent monitoring to risk stratify for relapse post-CART

2 years

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after CART therapy

1 year

What Are the Treatments Tested in This Trial?

Interventions

• NGS testing

Trial Overview The study tests if regular blood and bone marrow NGS testing after CART therapy can predict relapse in B-ALL patients. It aims to determine the necessity of additional treatments like HCT by monitoring B-cell recovery.

How Is the Trial Designed?

Group I: 1/Intervention Experimental Treatment 1 Intervention

Systematic, frequent monitoring intervention to risk stratify pts for risk of relapse postCART

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Next-generation sequencing was used to identify leukemia-specific sequences after tisagenlecleucel therapy in patients with acute lymphoblastic leukemia, highlighting its potential for early detection of therapy failure.

Detecting residual disease at levels below one per million cells by day 28 post-therapy was linked to poorer outcomes, suggesting that this method could help identify patients who may need additional treatments like stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rare Sequences Make Sense of CAR T-cell Therapy Outcomes. Ghorashian, S., Bartram, J.[2023]

Next-generation sequencing (NGS) has significantly advanced the understanding of acute lymphoblastic leukemia (ALL) by identifying novel molecular entities, which can improve diagnosis, risk stratification, and treatment planning.

Early efforts to use NGS for assessing minimal residual disease (MRD) in ALL show promise, highlighting the potential for personalized medicine approaches in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-Generation Sequencing in Acute Lymphoblastic Leukemia. Coccaro, N., Anelli, L., Zagaria, A., et al.[2020]

Minimal residual disease (MRD) is a crucial factor in predicting outcomes for acute lymphoblastic leukemia (ALL), and advancements in MRD detection methods have significantly improved cure rates across all age groups.

Next-generation sequencing (NGS) offers enhanced sensitivity and specificity for MRD detection compared to traditional RQ-PCR methods, and it provides valuable insights into the immune cell repertoire, although standardization of the NGS workflow is necessary before it can be widely implemented in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Next-Generation Sequencing the way to go for Residual Disease Monitoring in Acute Lymphoblastic Leukemia? Kotrova, M., Trka, J., Kneba, M., et al.[2018]

A comprehensive next-generation sequencing (NGS) assay was developed to detect various genetic abnormalities in acute lymphoblastic leukemia (ALL), including somatic mutations and copy number changes, demonstrating its clinical utility in patient evaluation.

The assay effectively identified single nucleotide variations (SNVs) and copy number variations (CNVs) simultaneously, which can simplify testing processes and aid in risk stratification for patients with high-risk mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of targeted NGS panel with comprehensive bioinformatics analysis for patients with acute lymphoblastic leukemia. Kim, B., Lee, H., Kim, E., et al.[2020]

Next-generation sequencing (NGS) is more sensitive than traditional methods like multiparametric flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) for detecting minimal residual disease (MRD) in children with acute lymphoblastic leukemia (ALL), identifying MRD in 57.5% of B-ALL and 80% of T-ALL cases after chemotherapy.

In B-ALL patients, having two or more clonal rearrangement sequences before treatment is linked to a higher likelihood of remaining positive for MRD after chemotherapy, indicating that NGS can help identify patients at greater risk for treatment failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application of next-generation sequencing-based monitoring of minimal residual disease in childhood acute lymphoblastic leukemia. Mai, H., Li, Q., Wang, G., et al.[2023]

In a study of 158 acute myeloid leukaemia samples, 16 lower-performance amplicons were identified in the TruSight Myeloid Sequencing Panel, including the gene CEBPA, which could affect diagnostic accuracy.

By using a different library preparation method (Nextera XT), researchers successfully increased the read depth for the CEBPA gene, demonstrating a way to improve sequencing results for genes with low performance in standard panels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coverage analysis in a targeted amplicon-based next-generation sequencing panel for myeloid neoplasms. Yan, B., Hu, Y., Ng, C., et al.[2022]

The study introduces a Vidjil add-on that allows for the analysis of NGS libraries prepared using the EuroClonality-NGS protocol, which is essential for assessing minimal residual disease in acute lymphoblastic leukemia.

Analysis results from Vidjil and ARResT/Interrogate showed a high level of agreement (r = 0.998) and low error rates, indicating that the Vidjil add-on is a reliable tool for processing these specific NGS libraries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vidjil add-on for MRD quantification of samples processed using the EuroClonality-NGS protocol. Giusti, GNN., Ribeiro, AV., Jotta, PY., et al.[2023]

The ALLseq next-generation sequencing panel effectively detects a wide range of genetic alterations in acute lymphoblastic leukemia (ALL), demonstrating 100% sensitivity and specificity, making it a reliable tool for clinical use.

This panel can provide clinically relevant information for over 83% of pediatric patients with ALL, aiding in diagnosis, risk assessment, and treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia. Gil, JV., Such, E., Sargas, C., et al.[2023]

Next-Generation Sequencing (NGS) is becoming an important tool for diagnosing and managing B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its complexity poses challenges for consistent clinical implementation across different laboratories.

A collaborative study among Spanish centers found that while various NGS panels performed well, each had unique advantages and drawbacks, highlighting the need for standardized analysis and reporting to improve result concordance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia. Vega-Garcia, N., Benito, R., Esperanza-Cebollada, E., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40330780/

The emerging role of next-generation sequencing in ... Next-generation sequencing (NGS) has emerged as a promising approach for MRD assessment, offering better sensitivity and the ability to track clonal evolution.

2. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1570041/full

The emerging role of next-generation sequencing in ... Next-generation sequencing (NGS) has emerged as a promising approach for MRD assessment, offering better sensitivity and the ability to track clonal evolution.

3. ashpublications.org ashpublications.org/blood/article/144/3/253/516077/How-I-use-next-generation-sequencing-MRD-to-plan

How I use next-generation sequencing–MRD to plan ... Early studies have shown superior results compared with MFC and suggest that NGS-MRD may allow for the determination of patients in whom reduced ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05621291

NCT05621291 | A Study to Evaluate Next-Generation ... A Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-cell Recovery to Guide Management Following Chimeric Antigen Receptor ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304383524004993

Measurable residual disease testing by next generation ... Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6627957/

Next-Generation Sequencing in Acute Lymphoblastic Leukemia The purpose of our review is to report the most recent discoveries obtained by NGS studies for ALL diagnosis, risk stratification, and treatment planning.

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00206-7/fulltext

Usefulness and real-world outcomes of next generation ... According to our data, real-world outcomes after NGS testing provide evidence of the benefit of clinical judgement in patients with either ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124055897

Poster Abstracts 614.Acute Lymphoblastic Leukemias NGS detects very low-level (<0.001%) residual clonal sequences in 22% of patients and the clinical significance remains a matter of ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/17474086.2024.2354922

Full article: Is next-generation sequencing the future of ... The 5-year RFS for patients who were PCR+/NGS- and PCR-/NGS- was 84% and 73%, respectively (p = 0.84), and 5-year OS was 94% and 80%, respectively (p = 0.87).