P1, N=47, Terminated, Arrowhead Pharmaceuticals | Phase classification: P1a/1b --> P1

Finally, a synergistic and additive effect was observed for OLE in combination with cytarabine, but not with cyclophosphamide. We may envisage that OLE may be used as a food supplement in B-ALL patients treated with cytarabine, taking advantage of the potentiated effect of chemotherapy, without additional side effects.

Antitumor efficacy in vivo was also observed with CML-07-119 in a mouse xenograft model engrafted with AML NOMO-1 cells, equivalent to the drug cytarabine...These structures revealed that the inhibitor occupies a previously proposed product inhibitory channel of the enzyme, and modulates previously unknown conformational states of GGPPS quaternary structure. This work validates GGPPS inhibition as potential novel mechanism for the treatment of AML.

In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www.

P4, N=140, Recruiting, Peking University Third Hospital | Not yet recruiting --> Recruiting

We demonstrated that SC significantly reduced cell proliferation, decreased SIRT1 levels, increased acetylated p53, activated cleaved caspase-3, and enhanced apoptosis in cytarabine-resistant cells. These findings suggest that SC might have potential as a therapeutic adjuvant for AML, providing efficacy in chemoresistant cases compared with cytarabine treatment alone.

Metagenomic next-generation sequencing of biopsy tissue revealed HBV, confirming a concurrent pulmonary HBV infection. Treatment with methylprednisolone, rituximab, and entecavir resulted in a favorable outcome.

Due to transaminitis, high-dose methotrexate therapy was deferred, and the patient was initiated on intrathecal (IT) chemotherapy with methotrexate and cytarabine. Following five cycles of IT chemotherapy, the patient's neurologic status significantly improved, and CSF analysis showed resolution of the atypical T-cell population. This case highlights the rare occurrence of CNS progression of FMF, even in the absence of lymphatic involvement and with well-controlled skin manifestations, and underscores the role of IT chemotherapy in managing this complication.

P1/2, N=43, Suspended, SymBio Pharmaceuticals | Recruiting --> Suspended

Proteomic profiling showed that NAMPT inhibition with KPT-9274 induced adaptive upregulation of BCL2, an anti-apoptotic protein, highlighting a survival mechanism...Additionally, NAMPT inhibition reduced PARP activity and impaired DNA repair pathways, sensitizing AML cells to cytarabine and hypomethylating agents. Together, these results demonstrate that NAMPT inhibition both potentiates venetoclax activity and enhances the cytotoxic effects of standard chemotherapies by targeting metabolic and DNA repair vulnerabilities. These findings provide strong preclinical support for evaluating NAMPT and BCL2 dual inhibition strategies in future AML clinical trials.

Cytarabine (ara-C) and fludarabine (F-ara-A) are key drugs in leukaemia treatment. Mechanistically, IMPDHi depleted allosteric SAMHD1 activators GTP and dGTP, thereby increasing active triphosphate metabolites in SAMHD1-proficient, but not SAMHD1-deficient, cells. Our findings suggest that the addition of IMPDHi to ara-C and F-ara-A may have therapeutic benefits in some AML cases.

For relapsed and refractory APL, relevant drug resistance gene monitoring should be carried out. Some relapsed and refractory APL patients who do not respond to conventional treatment are at risk of death. We report a successful case, the regimen of VEN targeted therapy combined with chemotherapy still holds promise for the treatment of future relapsed/refractory APL.