A Phase I/II Trial of MEC (Mitoxantrone, Etoposide, Cytarabine) in Combination with Ixazomib for Relapsed Refractory Acute Myeloid Leukemia
| العنوان: | A Phase I/II Trial of MEC (Mitoxantrone, Etoposide, Cytarabine) in Combination with Ixazomib for Relapsed Refractory Acute Myeloid Leukemia |
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| المؤلفون: | Matt Kalaycio, Benjamin Tomlinson, Alexander Miron, Betty K. Hamilton, Aaron T. Gerds, Valeria Visconte, Hetty E. Carraway, Paul Elson, Paolo Caimi, Sudipto Mukherjee, Aziz Nazha, Jennifer S. Carew, John J. Pink, Ronald Sobecks, Ehsan Malek, Anjali S. Advani, Marcos de Lima, Jane A. Little, Brenda W. Cooper, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Ricky Chan, Wei Wei, Allison Unger |
| المصدر: | Clinical Cancer Research. 25:4231-4237 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Boron Compounds, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, Population, Glycine, Article, Ixazomib, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, education, Etoposide, Aged, Salvage Therapy, Mitoxantrone, education.field_of_study, business.industry, Remission Induction, Cytarabine, Myeloid leukemia, Middle Aged, Leukemia, Myeloid, Acute, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, chemistry, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Proteasome inhibitor, Female, Patient Safety, Bone marrow, Neoplasm Recurrence, Local, business, medicine.drug |
| الوصف: | Purpose: The prognosis of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) remains poor, and novel therapies are needed. The proteasome pathway represents a potential therapeutic target. A phase I trial of the second-generation proteasome inhibitor ixazomib in combination with MEC (mitoxantrone, etoposide, and cytarabine) was conducted in patients with R/R AML. Patients and Methods: Dose escalation of ixazomib was performed using a standard 3 × 3 design. Gene-expression profiling was performed on pretreatment and posttreatment bone marrow or blood samples. Results: The maximum tolerated dose of ixazomib in combination with MEC was 1.0 mg. The dose limiting toxicity was thrombocytopenia. Despite a poor risk population, the response rate [complete remission (CR)/CR with incomplete count recovery (CRi)] was encouraging at 53%. Gene-expression analysis identified two genes, IFI30 (γ-interferon inducible lysosomal thiol reductase) and RORα (retinoic orphan receptor A), which were significantly differentially expressed between responding and resistant patients and could classify CR. Conclusions: These results are encouraging, but a randomized trial is needed to address whether the addition of ixazomib to MEC improves outcome. Gene-expression profiling also helped us identify predictors of response and potentially novel therapeutic targets. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49ee1e544309ae87e0a585afb4f26642Test https://doi.org/10.1158/1078-0432.ccr-18-3886Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....49ee1e544309ae87e0a585afb4f26642 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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