A Phase 1/2 Dose Evaluation and Cohort Expansion Study of the Safety and Efficacy of Anti-CD70 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX131) in Adult Subjects With Relapsed/Refractory Hematologic Malignancies

This is an open label, multicenter, phase 1/2 dose evaluation and cohort expansion study evaluating the safety and efficacy of CTX131 in subjects with Relapsed/Refractory Hematologic Malignancies

开始日期2024-08-13

申办/合作机构

CRISPR Therapeutics AG

ChiCTR2100044308

/ Recruiting早期临床1期IIT

Flumatinib combined with chemotherapy for elderly Philadelphia chromosome/BCR-ABL1 positive acute lymphoblastic leukemia: a prospective study

开始日期2021-02-27

申办/合作机构-

100 项与 BCR-ABL1阳性急性淋巴细胞白血病相关的临床结果

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100 项与 BCR-ABL1阳性急性淋巴细胞白血病相关的转化医学

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0 项与 BCR-ABL1阳性急性淋巴细胞白血病相关的专利（医药）

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373

项与 BCR-ABL1阳性急性淋巴细胞白血病相关的文献（医药）

2025-03-01·SAGE Open Medical Case Reports

Periorbital edema and phototoxic rash associated with dasatinib: A case report

Article

作者: Ugurlu, Bera Omer ; Malkan, Umit Yavuz

Dasatinib is an effective agent in the treatment of bcr-abl positive acute lymphoblastic leukemia and chronic myeloid leukemia cases. Various skin reactions may occur when tyrosine kinase inhibitors are used. The severity of side effects increases in phototoxic reactions with sunlight. In this case, a phototoxic rash that developed in a 78-year-old bcr-abl positive acute lymphoblastic leukemia patient is presented. This case supports that phototoxic reactions may occur with dasatinib and emphasizes that clinicians should be alert for this side effect.

2025-02-25·Theranostics

CD19-targeted HSP90 inhibitor nanoparticle combined with TKIs reduces tumor burden and enhances T-cell immunity in murine B-cell malignancies

Article

作者: Ren, Juan ; Liu, Huashen ; Qin, Mengting ; Shi, Mengxin ; Chen, Xiaodong ; Zhang, Mingzhen ; Zhou, Wen ; Zhang, Weile ; Zhang, Shuyuan ; Ji, Yanhong ; Ma, Yunfeng ; Yang, Mei

Rationale: Conventional chemotherapies for B-cell malignancies are often limited by drug resistance and significant side effects due to non-specific targeting. This research aimed to improve treatment efficacy by developing nano-delivery systems that specifically target tumor cells, thereby enhancing therapeutic precision and reducing off-target toxicity. Methods: The construction, biocompatibility, and targeting capability of CD19@NP/17-DMAG were evaluated using TEM, HPLC, FTIR spectroscopy, CCK-8 assay, flow cytometry (FC), and IVIS imaging. Therapeutic efficacy was assessed through Western blotting, RT-qPCR, flow cytometry, H&E staining, BrdU assay, and apoptosis assays. The mechanism of action of CD19@NP/17-DMAG in murine B-cell malignancies was investigated using RNA sequencing, in vivo T-cell depletion, and CRISPR/Cas9 technology. Results: CD19@NP/17-DMAG nanoparticles demonstrated enhanced efficacy in murine models of BCR-ABL1⁺ B-cell acute lymphoblastic leukemia (B-ALL) when combined with tyrosine kinase inhibitors (TKIs), including the BCR-ABL1-targeted imatinib and the broad-spectrum ponatinib. This combination significantly reduced tumor burden, prolonged survival, and induced a robust anti-tumor T-cell response. RNA-seq analysis indicated that the targeted treatment modulated genes related to cell proliferation, apoptosis, and antigen presentation. Notably, this treatment also increased MHC class I (MHC-I) expression, thereby strengthening antigen presentation in BCR-ABL1⁺ B-ALL cells. Ponatinib-based therapy achieved complete remission, eradicated minimal residual disease, and established long-term immune memory in BCR-ABL1⁺ B-ALL. In addition, CD19@NP/17-DMAG was effective in another B-cell malignancy model, A20 lymphoma, significantly slowing tumor growth and amplifying T-cell responses. Conclusions: These findings highlight the CD19@NP/17-DMAG system as a promising therapeutic approach that both augments T cell immune responses and minimizes side effects in B-cell malignancies.

2024-12-01·British Journal of Haematology

Efficacy and safety of olverembatinib in adult BCR::ABL1‐positive ALL with T315I mutation or relapsed/refractory disease

Article

作者: Liu, Yuanfang ; Tang, Sijie ; Chen, Saijuan ; Ren, Jiayi ; Wang, Cheng ; Ouyang, Wanyan ; Peng, Lijun ; Weng, Xiangqin ; Hao, Jie ; Wang, Jin ; Liu, Weiyang ; Mi, Jian‐Qing ; Jing, Duohui ; Zhu, Yongmei

SummaryThird‐generation tyrosine kinase inhibitors (TKIs) have much potential for the treatment of BCR::ABL1‐positive leukaemia, particularly that harbouring the ABL1 T315I mutation. Olverembatinib (HQP1351), a novel third‐generation TKI, has favourable efficacy and safety profiles in chronic myeloid leukaemia. Here, we present the clinical findings from 31 BCR::ABL1‐positive acute lymphoblastic leukaemia (ALL) patients who received olverembatinib. Among the 14 patients with overt relapsed/refractory (R/R) disease (including 10 with the T315I mutation), 71.4% achieved an overall response. Of the other 17 patients with minimal residual disease (MRD)‐positive ALL (including 14 with the T315I mutation), 60.0% and 47.1% achieved MRD flow negativity and complete molecular remission, respectively. With a median follow‐up time of 16.3 months, the median event‐free survival and overall survival were 3.9 and 8.3 months respectively, in overt R/R patients, and 11.5 and 18.4 months in MRD‐positive patients. Allogeneic haematopoietic stem cell transplantation further improved outcomes among responders. The safety profile was generally manageable. This study suggests that olverembatinib‐based therapy is another promising option for BCR::ABL1‐positive ALL in addition to ponatinib, especially for patients with MRD‐positive disease and a single T315I mutation.

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