A Randomized International Phase 3 Trial of Imatinib and Chemotherapy With or Without Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like ABL-Class B-Cell Acute Lymphoblastic Leukemia

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

开始日期2025-02-28

申办/合作机构

National Cancer Institute

100 项与 c-Kit x Bcr-Abl x SRC x PDGFRβ x EphA2 相关的临床结果

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100 项与 c-Kit x Bcr-Abl x SRC x PDGFRβ x EphA2 相关的转化医学

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0 项与 c-Kit x Bcr-Abl x SRC x PDGFRβ x EphA2 相关的专利（医药）

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项与 c-Kit x Bcr-Abl x SRC x PDGFRβ x EphA2 相关的文献（医药）

2013-10-01·The Oncologist2区 · 医学

Phase II Study of Dasatinib (BMS-354825) in Patients With Metastatic Adenocarcinoma of the Pancreas

2区 · 医学

Article

作者: Krishnamurthi, Smitha ; Fu, PingFu ; Brell, Joanna ; O'Brien, Timothy ; Bergman, Mark ; Chee, Cheng Ean ; Meropol, Neal J. ; Wright, John J. ; Reese, Amy ; Gibbons, Joseph ; Nock, Charles J. ; Bokar, Joseph ; Gudena, Vinay ; Dowlati, Afshin ; Saltzman, Joel ; Teston, Lois

AbstractBackground.Src, EphA2, and platelet-derived growth factor receptors α and β are dysregulated in pancreatic ductal adenocarcinoma (PDAC). Dasatinib is an oral multitarget tyrosine kinase inhibitor that targets BCR-ABL, c-Src, c-KIT, platelet-derived growth factor receptor β, and EphA2. We conducted a phase II, single-arm study of dasatinib as first-line therapy in patients with metastatic PDAC.Methods.Dasatinib (100 mg twice a day, later reduced to 70 mg twice a day because of toxicities) was orally administered continuously on a 28-day cycle. The primary endpoint was overall survival (OS). Response was measured using the Response Evaluation Criteria in Solid Tumors. Circulating tumor cells (CTCs) were also collected.Results.Fifty-one patients enrolled in this study. The median OS was 4.7 months (95% confidence interval [CI]: 2.8–6.9 months). Median progression-free survival was 2.1 months (95% CI: 1.6–3.2 months). In 34 evaluable patients, the best response achieved was stable disease in 10 patients (29.4%). One patient had stable disease while on treatment for 20 months. The most common nonhematologic toxicities were fatigue and nausea. Edema and pleural effusions occurred in 29% and 6% of patients, respectively. The number of CTCs did not correlate with survival.Conclusion.Single-agent dasatinib does not have clinical activity in metastatic PDAC.

2011-08-01·Journal of Neuro-Oncology2区 · 医学

Retrospective study of dasatinib for recurrent glioblastoma after bevacizumab failure

2区 · 医学

Article

作者: D. C. LaFrankie ; C. Lu-Emerson ; A. D. Norden ; P. Y. Wen ; R. Beroukhim ; S. Ruland ; E. C. Quant ; L. M. Doherty ; J. Drappatz ; A. S. Ciampa

There is no effective treatment for recurrent glioblastoma (GBM) after bevacizumab failure. Putative mechanisms of resistance to bevacizumab include increased pericyte coverage, mediated partly by platelet-derived growth factor receptor (PDGFR) signaling, and an infiltrative tumor growth pattern potentially dependent on SRC. We explored the efficacy of dasatinib, a SRC, BCR-ABL, c-KIT, EPHA2, and PDGFRβ inhibitor, in patients with recurrent GBM after bevacizumab failure. Adult patients with histologically confirmed GBM who failed bevacizumab therapy were treated with dasatinib 70-100 mg twice daily in combination with bevacizumab (n = 14), until tumor progression or unacceptable toxicity. Fourteen patients were treated. Median age was 55 years (range 32-66) and median KPS was 80 (range 50-90). All patients (100%) had glioblastomas. The median number of prior regimens was 4 (range from 2 to 6). Of the thirteen evaluable patients, none had a complete or partial response. Only one patient had stable disease after an 8 week interval. Median progression-free survival (PFS) was 28 days (95% confidence interval [CI] 26-35 days). Six month progression-free survival (PFS6) was 0%. Median overall survival (OS) was 78 days (95% CI 41-137 days). Treatment was moderately well-tolerated, although one patient sustained a grade 4 intracerebral hemorrhage. Dasatinib in conjunction with bevacizumab does not appear to have activity in patients with recurrent, heavily pretreated GBM.