B Acute Lymphoblastic Leukemia

Rituximab combined with CAR-T therapy is effective for improving the long-term prognosis of B-ALL patients who have failed multiple lines of therapy. In vitro, we observed that rituximab potentially improves CAR-T efficacy by sensitizing ALL to CART-mediated cytotoxicity and reducing CAR-T exhaustion.

P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Jul 2024

P3, N=680, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Jul 2024

CAR-T therapy followed by allo-HSCT can be a safe and effective treatment for Ph-positive B-ALL pediatric patients.

P2, N=20, Recruiting, The First Affiliated Hospital of Soochow University | Not yet recruiting --> Recruiting | Initiation date: Oct 2023 --> Apr 2024

P1/2, N=20, Completed, Celgene | Recruiting --> Completed | N=121 --> 20 | Trial completion date: Dec 2024 --> Jan 2024 | Trial primary completion date: Dec 2024 --> Jan 2024

The findings prompt reflection also on the broader role of epigenetics in decoupling of replication from lineage differentiation activation by the B cell lineage master transcription factor hub. Such oncogenesis and resistance mechanisms, being predictable and epigenetic, offer practical opportunities for intervention, potentially non-cross-resistant and safe vis-à-vis present cytotoxic and CAR-T treatments.

Our research proved shared genetic architecture between autoimmune disorders and B-ALL and shed light on the potential mechanism that might involve in.

P=N/A, N=60, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

No abstract available

Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.

In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

P3, N=310, Suspended, Alliance for Clinical Trials in Oncology | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P=N/A, N=353, Recruiting, Beijing GoBroad Hospital | Not yet recruiting --> Recruiting

Overall, these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

By targeting BCL2, a driver within the pre-pro-B-like cell signaling network, we find that venetoclax significantly potentiates asparaginase efficacy in vitro and in vivo. These findings demonstrate a single-cell systems pharmacology framework to predict effective combination therapies based on intra-leukemia heterogeneity in developmental state, with potentially broad applications beyond B-ALL.

The introduction of rituximab has improved the outcomes in CD20 positive cases. Other monoclonal antibodies, such as tafasitamab (anti-CD19), obinutuzumab (anti-CD20) and epratuzumab (anti-CD22) have been tested in trials (NCT05366218, NCT04920968, NCT00098839)...In contrast to ATP site inhibitors such as dasatinib and ponatinib, the novel first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor asciminib did not significantly impact ADCC in our settings. Our results suggest that asciminib should be considered in clinical trials.

P1, N=55, Terminated, Fred Hutchinson Cancer Center | Active, not recruiting --> Terminated; Terminated due to slow enrollment and end of funding

Tyrosine kinase/cytokine-receptor rearrangements were detected in 7% of BCP-LBL. These results indicate that genetic subtypes can be identified in BCP-LBL using next-generation sequencing, even on FFPE tissue, and may be relevant to guide treatment.

P2, N=80, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting

Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.

Four cases relapsed in the lately 3 years were RAS signaling pathway mutation-positive. RAS signaling pathway mutation is an important biomarker for poorer relapse-free survival in pediatric B-ALL patients despite good early MRD levels.

Moreover, several aberrant markers, such as CD2, CD56, CD7, and CD117, were rarely expressed in the B-ALL samples, and if expressed, they were enriched in specific genetic subtypes. The results of this study indicate that immunophenotypic features are correlated with specific genetic subtypes of childhood B-ALL.

P1/2, N=75, Not yet recruiting, Essen Biotech | Initiation date: Feb 2024 --> Nov 2024

P=N/A, N=353, Not yet recruiting, Beijing GoBroad Hospital

P2, N=35, Completed, Chen Suning | Active, not recruiting --> Completed

Integrated machine learning identified the high-risk cells for disease free survival, and overall survival, while simulation of ACT therapy using CXCR6+CD4+T cells indicated that CXCR6+CD4+ T cells could remodel the bone marrow microenvironments towards anti-tumor. Based on the expression of genes involved in formation of resident memory T cells, CXCR6 is not a marker of resident memory CD4+T cells but defines therapeutic subtypes of CD4+ cytotoxic T cell lineage for pediatric B-ALL.

After considering transplantation, high ECM1 transcription level was not an independent risk factor, although OS was still poor (low vs. high, 71.1% vs. 56.8%, P = 0.038). Our findings suggested that ECM1 may be a potential molecular marker for diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction of B cell ALL.Trial registration Trial Registration Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTR-OPC-14005546]; http://www.chictr.org.cn .

DNR induces Cyr61 production in B-ALL cells, and increased Cyr61 levels reduce the chemosensitivity of B-ALL cells. Consequently, targeting Cyr61 or related ATM signaling pathway may present a promising treatment strategy to enhance the chemosensitivity of patients with B-ALL.

Grade 2 and 4 graft-versus-host disease occurred in two patients. Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Our findings highlight the importance of defining the basis of CD22 escape, and eradication of residual disease prior to HSCT. The identified mechanisms of escape from CD22-targeted therapy extend beyond antigen loss, and provide opportunities to improve therapeutic approaches and overcome resistance.

We also report an interesting case of a patient with PAX5::FKBP15 and a pathogenic variant in PTPN11 who underwent an early relapse with a monocytic switch. In conclusion, this study provides valuable insights into the presence, frequency, and prognostic significance of diverse PAX5 alterations in B-ALL patients, highlighting the complexity of genetic factors and their impact on patient outcomes.

Although IL-15 level adaptation in the REG and the CG performed similarly, the REG induced a better clinical outcome. Resistance exercises may help improve survival prognosis and reduce relapses in patients with ALL.

P2, N=16, Active, not recruiting, National Cancer Institute (NCI)

In vivo experiments also confirmed that overexpression of miR-539-5p significantly inhibited BMP2 to suppress Treg activation and Smad1 and Smad2 phosphorylation, and finally inhibit the B-ALL process. In conclusion, miR-539-5p was significantly under-expressed in B-ALL and could target BMP2 to promote its expression, and the overexpressed BMP2 further promoted Treg activation in B-ALL by regulating TGF-β/Smads/MAPK pathway.

No abstract available

P1, N=48, Not yet recruiting, Beijing GoBroad Hospital

P1, N=150, Recruiting, Nkarta Inc. | Trial primary completion date: Dec 2023 --> Aug 2024

At the 65th Annual Meeting of the American Society of Hematology (ASH) 2023, which took place in San Diego, California, from December 9-12, 2023, new results from different trials were reported by different research groups. We provide a summary of the latest progress in BsAbs for immunotherapy in adult acute leukemia.

No abstract available

P2, N=78, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting

P2, N=171, Not yet recruiting, National Cancer Institute (NCI)