A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma
Copyright© 2018 Ferrata Storti Foundation..
This phase I/II dose-escalation study investigated the all-oral ixazomib-melphalan-prednisone regimen, followed by single-agent ixazomib maintenance, in elderly, transplant-ineligible patients with newly diagnosed multiple myeloma. Primary phase I objectives were to determine the safety and recommended phase II dose of ixazomib-melphalan-prednisone. The primary phase II objective was to determine the complete plus very good partial response rate. In phase I, patients were enrolled to 4 arms investigating weekly or twice-weekly ixazomib (13 28-day cycles or nine 42-day cycles) plus melphalan-prednisone. In phase II, an expansion cohort was enrolled at the recommended phase II ixazomib dose. Of the 61 patients enrolled, 26 received the recommended phase II dose (ixazomib 4.0 mg [days 1, 8, 15] plus melphalan-prednisone 60 mg/m2 [days 1-4], 28-day cycles). Of the 61 enrolled patients, 36 (13 of 26 in the recommended phase II dose cohort) received single-agent ixazomib maintenance (days 1, 8, 15; 28-day cycles). In phase I, 10/38 patients reported dose-limiting toxicities in cycle 1, including grade 3 and/or 4 neutropenia (n=6) and thrombocytopenia (n=4). Complete plus very good partial response rate was 48% (48% at recommended phase II dose), including 28% (22%) complete response or better; responses deepened during maintenance in 34% (33%) of evaluable patients. After median follow up of 43.6 months, median progression-free survival was 22.1 months. Adverse events were mainly hematologic events, gastrointestinal events, and peripheral neuropathy. This study demonstrates the feasibility, tolerability, and activity of ixazomib-melphalan-prednisone induction and single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma patients. clinicaltrials.gov identifier 01335685.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:103 |
|---|---|
| Enthalten in: |
Haematologica - 103(2018), 9 vom: 28. Sept., Seite 1518-1526 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
San-Miguel, Jesús F [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.09.2019 Date Revised 11.09.2019 published: Print-Electronic ClinicalTrials.gov: NCT01335685 Citation Status MEDLINE |
|---|
| doi: |
10.3324/haematol.2017.185991 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM285981129 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM285981129 | ||
| 003 | DE-627 | ||
| 005 | 20231225050628.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3324/haematol.2017.185991 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0953.xml |
| 035 | |a (DE-627)NLM285981129 | ||
| 035 | |a (NLM)29954932 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a San-Miguel, Jesús F |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma |
| 264 | 1 | |c 2018 | |
| 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 11.09.2019 | ||
| 500 | |a Date Revised 11.09.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT01335685 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© 2018 Ferrata Storti Foundation. | ||
| 520 | |a This phase I/II dose-escalation study investigated the all-oral ixazomib-melphalan-prednisone regimen, followed by single-agent ixazomib maintenance, in elderly, transplant-ineligible patients with newly diagnosed multiple myeloma. Primary phase I objectives were to determine the safety and recommended phase II dose of ixazomib-melphalan-prednisone. The primary phase II objective was to determine the complete plus very good partial response rate. In phase I, patients were enrolled to 4 arms investigating weekly or twice-weekly ixazomib (13 28-day cycles or nine 42-day cycles) plus melphalan-prednisone. In phase II, an expansion cohort was enrolled at the recommended phase II ixazomib dose. Of the 61 patients enrolled, 26 received the recommended phase II dose (ixazomib 4.0 mg [days 1, 8, 15] plus melphalan-prednisone 60 mg/m2 [days 1-4], 28-day cycles). Of the 61 enrolled patients, 36 (13 of 26 in the recommended phase II dose cohort) received single-agent ixazomib maintenance (days 1, 8, 15; 28-day cycles). In phase I, 10/38 patients reported dose-limiting toxicities in cycle 1, including grade 3 and/or 4 neutropenia (n=6) and thrombocytopenia (n=4). Complete plus very good partial response rate was 48% (48% at recommended phase II dose), including 28% (22%) complete response or better; responses deepened during maintenance in 34% (33%) of evaluable patients. After median follow up of 43.6 months, median progression-free survival was 22.1 months. Adverse events were mainly hematologic events, gastrointestinal events, and peripheral neuropathy. This study demonstrates the feasibility, tolerability, and activity of ixazomib-melphalan-prednisone induction and single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma patients. clinicaltrials.gov identifier 01335685 | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Boron Compounds |2 NLM | |
| 650 | 7 | |a ixazomib |2 NLM | |
| 650 | 7 | |a 71050168A2 |2 NLM | |
| 650 | 7 | |a Melphalan |2 NLM | |
| 650 | 7 | |a Q41OR9510P |2 NLM | |
| 650 | 7 | |a Glycine |2 NLM | |
| 650 | 7 | |a TE7660XO1C |2 NLM | |
| 650 | 7 | |a Prednisone |2 NLM | |
| 650 | 7 | |a VB0R961HZT |2 NLM | |
| 700 | 1 | |a Echeveste Gutierrez, Maria-Asunción |e verfasserin |4 aut | |
| 700 | 1 | |a Špicka, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Mateos, María-Victoria |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Craig, Michael D |e verfasserin |4 aut | |
| 700 | 1 | |a Bladé, Joan |e verfasserin |4 aut | |
| 700 | 1 | |a Hájek, Roman |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Di Bacco, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Estevam, Jose |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Neeraj |e verfasserin |4 aut | |
| 700 | 1 | |a Byrne, Catriona |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Vickie |e verfasserin |4 aut | |
| 700 | 1 | |a van de Velde, Helgi |e verfasserin |4 aut | |
| 700 | 1 | |a Lonial, Sagar |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Haematologica |d 1947 |g 103(2018), 9 vom: 28. Sept., Seite 1518-1526 |w (DE-627)NLM000081892 |x 1592-8721 |7 nnns |
| 773 | 1 | 8 | |g volume:103 |g year:2018 |g number:9 |g day:28 |g month:09 |g pages:1518-1526 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3324/haematol.2017.185991 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 103 |j 2018 |e 9 |b 28 |c 09 |h 1518-1526 | ||