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Phase 1/2 study of DFP-10917 administered by continuous intravenous infusion in patients with recurrent or refractory acute myeloid leukemia.
- Source :
-
Cancer (0008543X) . May2019, Vol. 125 Issue 10, p1665-1673. 9p. - Publication Year :
- 2019
-
Abstract
- <bold>Background: </bold>DFP-10917, a deoxycytidine nucleoside analogue, has a unique mechanism of action resulting in leukemic cell death when administered for prolonged periods at low doses. The current phase 1/2 study investigated the safety, maximum tolerated dose, and evidence of antileukemic activity for DFP-10917 administered by 7-day or 14-day continuous intravenous infusion in patients with recurrent or refractory acute myeloid leukemia (AML).<bold>Methods: </bold>In the phase 1 dose escalation portion of the study, patients were administered DFP-10917 by 7-day continuous intravenous infusion plus 21-day rest (stage 1) or 14-day continuous intravenous infusion plus 14-day rest (stage 2). The primary objectives of phase 1 were to determine the maximum tolerated dose, the phase 2 dose, and the dose-limiting toxicities (DLTs) of DFP-10917. The primary objectives of phase 2 were to evaluate the overall response rate of DFP-10917 using complete response (CR), CR without platelet recovery (CRp), CR with incomplete blood count recovery (CRi) or partial response.<bold>Results: </bold>In stage 1 of phase 1 (4-35 mg/m2 /day as a 7-day continuous intravenous infusion), a DLT of grade 3 diarrhea occurred at a dose of 35 mg/m2 /day. In stage 2 of phase 1, a dose of 10 mg/m2 /day as a 14-day continuous intravenous infusion resulted in DLTs of prolonged hypocellularity, abdominal pain, diarrhea, and vomiting. The dose of 6 mg/m2 /day as a 14-day continuous intravenous infusion was found to be well tolerated and was selected for phase 2. Response rates in patients in phase 2 (N = 29) were 20.7% CR, 3.4% CRp, and 24.1% CRi. The overall response rate was 48.3% (95% confidence interval, 29.4%-67.5%).<bold>Conclusions: </bold>DFP-10917 as a 14-day continuous intravenous infusion at a dose of 6 mg/m2 /day can be administered safely and appears to be effective in patients with recurrent or refractory AML. A phase 3 investigation comparing DFP-10917 monotherapy versus standard of care in an early recurrent or refractory AML setting is warranted. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ACUTE myeloid leukemia
*INTRAVENOUS therapy
*BONE marrow
Subjects
Details
- Language :
- English
- ISSN :
- 0008543X
- Volume :
- 125
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Cancer (0008543X)
- Publication Type :
- Academic Journal
- Accession number :
- 136089710
- Full Text :
- https://doi.org/10.1002/cncr.31923