Acute Lymphocytic Leukemia

P1/2, N=20, Recruiting, University Hospital Tuebingen | Trial completion date: Mar 2027 --> Feb 2029 | Trial primary completion date: Mar 2027 --> Jul 2028

These findings suggest that Ag-NPs may enhance upstream signaling and drug response rather than directly acting on apoptotic proteins, supporting their potential as nanotechnological co-therapeutics in B-cell ALL. Further mechanistic and in vivo studies are warranted.

Consistent with prior preclinical studies, we demonstrate that dasatinib and ponatinib, unlike SRC sparing TKIs (imatinib, nilotinib), antagonize blinatumomab's T-cell engaging efficacy by potently inhibiting LCK Y394 phosphorylation, a critical step in proximal TCR signaling. We show that TKI-induced T-cell suppression and antagonism can be significantly improved by supplementing co-cultures with common gamma-chain cytokines, particularly IL-7. IL-7 robustly enhances human T-cell proliferation, reduces exhaustion, and significantly improves blinatumomab's cytotoxic efficacy in the presence of Src/BCRABL1 TKIs.

P2, N=30, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2026 --> Jul 2027 | Trial primary completion date: Jul 2026 --> Jul 2027

P1/2, N=50, Not yet recruiting, Novartis Pharmaceuticals

Additionally, the integration of IKZF1 deletion status into risk stratification models revealed markedly different survival outcomes, highlighting its potential interest in developing new stratification algorithms. These results underscore the critical importance of molecular profiling, particularly IKZF1 status, for improving outcomes in ALL patients in Tunisia.

P1/2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=80 --> 30

P=N/A, N=300, Recruiting, Chinese University of Hong Kong | N=150 --> 300 | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

Successive generations of TKIs have transformed Ph + ALL from a uniformly fatal leukemia into a highly treatable disease, with dasatinib or ponatinib-based and TKI-blinatumomab regimens achieving high rates of complete molecular remission...Novel agents, including asciminib and olverembatinib, are expanding options for resistant or relapsed disease, while CAR-T cell therapy and next-generation bispecific T-cell engagers are emerging as promising tools for refractory and post-TKI settings...Integrating potent TKIs with immunotherapy enables deep and durable remissions, potentially eliminating the need for upfront transplantation in selected patients. Future research should define molecular predictors of treatment-free remission, optimize CNS prophylaxis in targeted regimens, and establish standardized monitoring for safe TKI discontinuation.

To overcome these limitations, we systematically evaluated the synergistic Combination effects of three drug candidates, OTX-015 (BET inhibitor), Metformin (metabolic regulator), and Anlotinib (multitargeted tyrosine kinase inhibitor), with Chidamide. Chidamide and Anlotinib synergistically inhibit Hippo signaling pathway, which reveals a novel "dual epigenetic kinase targeting" strategy for the treatment of T-ALL. Future studies should validate these findings in vivo and investigate the impact of the metabolic microenvironment on therapeutic efficacy.

Importantly, MV-Blina did not induce either short- or long-term toxicity in in vitro neuronal models encompassing PBMCs, nor in immunocompromised CD46 transgenic mice, even under additional immunosuppression. Collectively, these findings support further investigations of MV-Blina as a potential treatment for patients with relapsed or refractory BCP-ALL.

Approximately 28% of patients carried TPMT and/or NUDT15 variants associated with non-wild-type enzymatic activity, increasing the risk of mercaptopurine-induced myelotoxicity. Preemptive genotyping is essential to reduce toxicity, optimize treatment, and advance precision medicine in this population. Additionally, the two TPMT variants p.G126A and p.D137Y, currently not classified within Clinical Pharmacogenetics Implementation Consortium-defined star alleles, highlight the need for functional validation and potential clinical classification to improve pharmacogenetic interpretation in diverse populations.