Back to Search
Start Over
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.
- Source :
-
Haematologica [Haematologica] 2018 Sep; Vol. 103 (9), pp. 1518-1526. Date of Electronic Publication: 2018 Jun 28. - Publication Year :
- 2018
-
Abstract
- 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/m <superscript>2</superscript> [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 .<br /> (Copyright© 2018 Ferrata Storti Foundation.)
- Subjects :
- Administration, Oral
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols adverse effects
Boron Compounds administration & dosage
Female
Glycine administration & dosage
Glycine therapeutic use
Humans
Induction Chemotherapy
Kaplan-Meier Estimate
Maintenance Chemotherapy
Male
Melphalan administration & dosage
Middle Aged
Multiple Myeloma diagnosis
Multiple Myeloma mortality
Neoplasm Metastasis
Neoplasm Staging
Prednisone administration & dosage
Treatment Outcome
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Boron Compounds therapeutic use
Glycine analogs & derivatives
Multiple Myeloma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 103
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 29954932
- Full Text :
- https://doi.org/10.3324/haematol.2017.185991