Chronic Myeloid Leukemia

P2, N=135, Completed, Fred Hutchinson Cancer Center | Active, not recruiting --> Completed

P2, N=34, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Feb 2025 --> Jun 2025

P=N/A, N=50, Not yet recruiting, Assiut University

P=N/A, N=81, Completed, Ann & Robert H Lurie Children's Hospital of Chicago | Unknown status --> Completed | N=200 --> 81

P2, N=130, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Dec 2029 --> Jan 2025

SLC variants can be predictive signals of imatinib responses among CML; Asian patients should be paid attention during the treatment.

P2, N=358, Not yet recruiting, Center for International Blood and Marrow Transplant Research

P2, N=20, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

YAP activators suppressed the growth of leukemia cells through induction of apoptosis. This suggested that YAP might function as a tumor suppressor in leukemia. SBP-3264 and XMU-MP-1 could be novel candidate molecular-targeted drugs for leukemia; however, further investigations are required.

P2, N=61, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2024

P2, N=144, Completed, Ascentage Pharma Group Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Aug 2024 | Trial primary completion date: Dec 2024 --> Aug 2024

Using the Ph translocation as an example, long read sequencing is shown to be a promising alternative method to detect SV, revolutionizing detection of chromosomal translocation to a higher precision. A more comprehensive spectrum of SV can be resolved along with cytogenetic results, enabling precise diagnosis and personalized monitoring of haematological malignancies.

This study compared responses of three commonly used CML cell lines (K562, LAMA84, KCL22) to five TKIs (imatinib, nilotinib, dasatinib, bosutinib, ponatinib) and a Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor commonly used in clinical settings. This comprehensive comparison provides valuable insights for refining preclinical models and enhancing translational relevance in CML research and treatment development. Understanding the diverse responses of CML cell lines to TKIs and STAMP inhibitor facilitates the selection of appropriate models for specific research questions, ultimately improving the accuracy and reliability of preclinical studies in CML.

Our results suggest that miR-188-5p acts as an oncomiRNA in CML pathogenesis and may be a promising therapeutic target for CML.

P1/2, N=34, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jun 2026 --> Jul 2025

The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis, and the mechanism may act through PI3K/AKT/mTOR signaling pathways.

P3, N=169, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Apr 2026 --> Mar 2024

This study revealed that bosutinib-induced elevation of serum creatinine, which was more pronounced in patients with the SLC22A2 808G/G genotype, does not indicate chronic kidney disease, but rather is simply a laboratory abnormality. If bosutinib-induced chronic kidney disease is suspected, renal function should be assessed by urinalysis and cystatin C levels to differentiate from simple elevation of serum creatinine.

Switching to second-line dasatinib treatment successfully overcame asciminib resistance and helped to achieve a deep molecular response. In case of treatment failures caused by single asciminib-specific point mutations, dasatinib therapy is a feasible choice.

NSC-66811 and Nutlin-3, MDM2 inhibitors, increased the percentage of Annexin-positive cells in K562/IR cells by 43 and 62% at concentrations of 10 and 25 µM, respectively. Additionally, pifithrin-α, a p53 inhibitor, suppressed MDM2 inhibitor-induced cell death in K562/IR cells. Overall, the findings of the present study highlight the therapeutic potential of MDM2 inhibitors for imatinib-resistant CML.

P1/2, N=52, Suspended, Uma Borate | Recruiting --> Suspended

P1, N=90, Active, not recruiting, Shenzhen TargetRx, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Sep 2026 | Trial primary completion date: Dec 2024 --> Mar 2026

P1, N=72, Active, not recruiting, Shenzhen TargetRx, Inc. | Not yet recruiting --> Active, not recruiting | Trial completion date: Feb 2025 --> Jul 2025

P2, N=40, Recruiting, Shenzhen TargetRx, Inc. | Not yet recruiting --> Recruiting | Trial completion date: Dec 2027 --> Apr 2028

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Jun 2025 --> Feb 2025

P=N/A, N=75, Recruiting, University of California, Irvine | Trial primary completion date: Dec 2024 --> Dec 2025

MLKL inactivation reduces such autophagy and renders the cells sensitive to autophagy inhibitors, such as homoharringtonine. Hence, MLKL inhibition creates a therapeutic vulnerability that could be utilized for CRC treatment.

Interestingly, STING expression was negatively correlated with TIDE biomarkers in AML, suggesting that AML patients with a high STING expression level may benefit from immunologic treatment. Our findings contribute a molecular characterization of STING across hematological malignancies, facilitating the development of individualized prognosis and treatment strategies.

P2, N=24, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=41 --> 24 | Trial completion date: Dec 2026 --> Feb 2026 | Trial primary completion date: Feb 2026 --> Feb 2025

P2, N=30, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Apr 2025

P2, N=102, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jul 2025

Our study indicates that in patients with a low BCR::ABL1 digital PCR result, a total TKI treatment duration of six or more years remains associated with a lower MolR rate and should generally be pursued. In patients treated for more than 6 years, BCR::ABL1 digital PCR was capable to identify stop candidates with a higher probability of TFR success.

P1, N=25, Recruiting, Mayo Clinic | Trial completion date: Mar 2027 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Jun 2027

Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (BCR-ABLi) are the mainstay of chronic myelogenous leukemia (CML) treatment...Dissecting the effects of pharmacological CDK8/19 inhibition on CML survival in response to BCR-ABLi, we found that a selective, non-toxic CDK8/19 inhibitor (CDK8/19i) Senexin B (SenB) and other CDK8/19i sensitized K562 cells to different BCR-ABLi via attenuation of cell cycle arrest...In contrast, IM-treated BCR-ABL-positive KU812 CML cells, which did not induce p27Kip1, readily died regardless of SenB treatment. Thus, CDK8/19i prevent the quiescence-mediated escape from BCR-ABLi-induced apoptosis, suggesting a strategy for avoiding the CML relapse.

Initial manifestation of CML with pelvic hematoma is uncommon and should undergo aspiration or drainage to avoid organization of hematoma and compressive symptoms locally.

This study demonstrates that CD26 CAR-M effectively targets and phagocytizes CD26-positive CML cells, implying that targeting CD26 with CAR-M could be a viable method for eradicating CML-LSCs. Furthermore, our discoveries illuminate the potential application of CAR-M in treating hematological malignancies.

P2, N=84, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Finally, by examining whether NCPs and all other CD66b+ neutrophil precursors are altered in representative hematological malignancies, we found that, in patients with chronic-phase chronic myeloid leukemia (CP-CML), but not with systemic mastocytosis (SM), there is an increased frequency of BM NCP4s, NCP6s, and all downstream CD45RA-negative neutrophil progenitors, suggesting their expansion in CML pathogenesis. Taken together, our data advance our knowledge of human neutropoiesis.

Asciminib has shown significant cytogenetic and molecular responses in heavily pretreated patients, those previously exposed to ponatinib, and treatment-naïve individuals, attributed to its pharmacological selectivity and generally favorable safety profile. This review provides an in-depth analysis of the preclinical and clinical evidence supporting the use of asciminib, synthesizing findings from a targeted literature search of PubMed and Web of Science. Our discussion integrates insights into its mechanism of action, clinical efficacy, safety, resistance patterns, and future directions.

P2, N=33, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

No abstract available

Moreover, the stability of these enzyme-ligand complexes was confirmed using molecular dynamics simulations. These findings suggested that compounds 1e and 1g can be considered promising cancer treatment agents.