A randomized phase II trial of CX-01 with standard therapy in elderly patients with acute myeloid leukemia (AML)
| Autor: | Stephen Marcus, Robert K. Stuart, Jonathan E. Kolitz, Matthew J. Wieduwilt, Don A. Stevens, Tibor Kovacsovics, Michael B. Maris, John L. Reagan, Paul J. Shami, Cecilia Arana-Yi, Moshe Yair Levy, Hana Safah, Michaela L. Tsai, Rachel J. Cook, Jay Yang, William B. Donnellan, Peter Westervelt |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty medicine.drug_class business.industry Anticoagulant Myeloid leukemia Heparin 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine medicine Heparin Derivative business Standard therapy 030215 immunology medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 37:7001-7001 |
| ISSN: | 1527-7755 0732-183X 0287-3338 |
| Popis: | 7001 Background: Elderly AML patients have poor outcomes irrespective of therapy. CX-01 is a low anticoagulant heparin derivative that retains heparin’s ability to alter the activity of the CXCL12/CXCR4 axis, P-selectin, extracellular histones, and Platelet Factor 4. A pilot study of CX-01 combined with standard therapy for AML led to a complete remission (CR) rate of 92% ( Blood Adv 2:381, 2018). We conducted a randomized, dose-finding study of the same combination in newly diagnosed elderly AML patients. Methods: 76 fit patients older than 59 were randomized to induction with idarubicin and cytarabine on a 7+3 schedule only (Group 1); 7+3 with a lower dose of CX-01 (0.125 mg/kg/hour) (Group 2); or 7+3 with a higher dose of CX-01 (0.25 mg/kg/hour) (Group 3). Patients in CR received consolidation therapy consisting of up to 3 cycles of intermediate dose cytarabine (1000 mg/m2 every 12 hours on Days 1, 3, 5) without or with the same dose of CX-01 for Groups 1, 2, and 3, respectively. CX-01 was given as a continuous infusion after a 4 mg/kg bolus until completion of chemotherapy. Results: 66 of 75 treated patients were evaluable for response. Ten patients were not evaluable due to withdrawal of consent (6 patients), introduction of midostaurin after its approval (3 patients), or death due to hepatic sinusoidal obstructive disease at Day 21 (1 patient in Group 2). We present results for evaluable patients and not on an intent to treat basis. Baseline characteristics were similar across groups. The composite CR rate (CR + CRi) was highest for patients in Group 3 with 89% patients achieving a composite CR as compared to 58% and 50% in Groups 1 and 2, respectively. Kaplan-Meier curves indicated a statistically significant improvement in event free survival (EFS) (P = 0.019) and a non-significant trend (P = 0.10) to improvement in OS in Group 3 as compared to Group 1. Groups 1 and 2 were comparable for EFS and OS. CX-01 was well tolerated without increased incidence of bleeding in Groups 2 and 3. Conclusions: The encouraging CR rate and EFS in elderly fit patients with newly diagnosed AML suggests that CX-01 may potentiate the efficacy of standard AML induction therapy. A randomized study to confirm these findings with the higher dose of CX-01 is warranted. Clinical trial information: NCT02873338. |
| Databáze: | OpenAIRE |
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