Aspacytarabine for the treatment of patients with AML unfit for intensive chemotherapy : a phase 2 study
© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved..
High-dose cytarabine is associated with gastrointestinal and cerebellar toxicity, precluding its use for older or unfit patients with acute myeloid leukemia (AML). Aspacytarabine, an inactive prodrug of cytarabine, was evaluated as monotherapy in a phase 2b study of patients unfit for intensive chemotherapy (NCT03435848). Sixty-five patients with AML were treated with aspacytarabine 4.5 g/m2 per day (equimolar to 3 g/m2 per day cytarabine) for 6 doses per treatment. The median age was 75 years; 60.6% of patients had de novo AML, 28.8% had AML secondary to myelodysplastic syndrome, and 10.6% had therapy-related AML. Overall, 36.9% achieved complete remission (CR) with full count recovery. CR rates in patients with secondary AML, patients with prior treatment with hypomethylating agents, and patients with TP53 mutation were 26.7%, 25%, and 36%, respectively. Median overall survival was 9 months (range, 6-15.9) and was not reached among responders. Hematologic recovery was observed in all responding patients by day 26 without prolonged cytopenias. Adverse events typically precluding the use of high-dose cytarabine in older or unfit patients were not observed. These data suggest that aspacytarabine may be an effective regimen with a reduction in the attendant toxicities associated with high-dose cytarabine, an important consideration when treating AML and other hematologic disorders that use high-dose cytarabine. This trial was registered at www.clinicaltrials.gov as #NCT03435848.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
|---|---|
| Enthalten in: |
Blood advances - 7(2023), 24 vom: 26. Dez., Seite 7494-7500 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Altman, Jessica K [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 10.01.2024 published: Print ClinicalTrials.gov: NCT03435848 Citation Status MEDLINE |
|---|
| doi: |
10.1182/bloodadvances.2023010943 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM363953094 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM363953094 | ||
| 003 | DE-627 | ||
| 005 | 20240114233805.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1182/bloodadvances.2023010943 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1256.xml |
| 035 | |a (DE-627)NLM363953094 | ||
| 035 | |a (NLM)37903324 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Altman, Jessica K |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aspacytarabine for the treatment of patients with AML unfit for intensive chemotherapy |b a phase 2 study |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.12.2023 | ||
| 500 | |a Date Revised 10.01.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03435848 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. | ||
| 520 | |a High-dose cytarabine is associated with gastrointestinal and cerebellar toxicity, precluding its use for older or unfit patients with acute myeloid leukemia (AML). Aspacytarabine, an inactive prodrug of cytarabine, was evaluated as monotherapy in a phase 2b study of patients unfit for intensive chemotherapy (NCT03435848). Sixty-five patients with AML were treated with aspacytarabine 4.5 g/m2 per day (equimolar to 3 g/m2 per day cytarabine) for 6 doses per treatment. The median age was 75 years; 60.6% of patients had de novo AML, 28.8% had AML secondary to myelodysplastic syndrome, and 10.6% had therapy-related AML. Overall, 36.9% achieved complete remission (CR) with full count recovery. CR rates in patients with secondary AML, patients with prior treatment with hypomethylating agents, and patients with TP53 mutation were 26.7%, 25%, and 36%, respectively. Median overall survival was 9 months (range, 6-15.9) and was not reached among responders. Hematologic recovery was observed in all responding patients by day 26 without prolonged cytopenias. Adverse events typically precluding the use of high-dose cytarabine in older or unfit patients were not observed. These data suggest that aspacytarabine may be an effective regimen with a reduction in the attendant toxicities associated with high-dose cytarabine, an important consideration when treating AML and other hematologic disorders that use high-dose cytarabine. This trial was registered at www.clinicaltrials.gov as #NCT03435848 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Cytarabine |2 NLM | |
| 650 | 7 | |a 04079A1RDZ |2 NLM | |
| 700 | 1 | |a Zuckerman, Tsila |e verfasserin |4 aut | |
| 700 | 1 | |a Koprivnikar, Jamie |e verfasserin |4 aut | |
| 700 | 1 | |a McCloskey, James |e verfasserin |4 aut | |
| 700 | 1 | |a Kota, Vamsi |e verfasserin |4 aut | |
| 700 | 1 | |a Keng, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Frankfurt, Olga |e verfasserin |4 aut | |
| 700 | 1 | |a Abaza, Yasmin |e verfasserin |4 aut | |
| 700 | 1 | |a Bixby, Dale L |e verfasserin |4 aut | |
| 700 | 1 | |a Emadi, Ashkan |e verfasserin |4 aut | |
| 700 | 1 | |a Burch, Micah |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatnagar, Bhavana |e verfasserin |4 aut | |
| 700 | 1 | |a Luger, Selina M |e verfasserin |4 aut | |
| 700 | 1 | |a Percival, Mary-Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Wolach, Ofir |e verfasserin |4 aut | |
| 700 | 1 | |a Craig, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Ganzel, Chezi |e verfasserin |4 aut | |
| 700 | 1 | |a Roboz, Gail |e verfasserin |4 aut | |
| 700 | 1 | |a Levi, Itai |e verfasserin |4 aut | |
| 700 | 1 | |a Gourevitch, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Flaishon, Liat |e verfasserin |4 aut | |
| 700 | 1 | |a Tessler, Shoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Blumberg, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Gengrinovitch, Stela |e verfasserin |4 aut | |
| 700 | 1 | |a Ben Yakar, Ruth |e verfasserin |4 aut | |
| 700 | 1 | |a Rowe, Jacob M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood advances |d 2016 |g 7(2023), 24 vom: 26. Dez., Seite 7494-7500 |w (DE-627)NLM268683263 |x 2473-9537 |7 nnns |
| 773 | 1 | 8 | |g volume:7 |g year:2023 |g number:24 |g day:26 |g month:12 |g pages:7494-7500 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1182/bloodadvances.2023010943 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 7 |j 2023 |e 24 |b 26 |c 12 |h 7494-7500 | ||