PMID- 25325301
OWN - NLM
STAT- MEDLINE
DCOM- 20150916
LR  - 20211021
IS  - 2044-5385 (Print)
IS  - 2044-5385 (Electronic)
IS  - 2044-5385 (Linking)
VI  - 4
IP  - 10
DP  - 2014 Oct 17
TI  - Phase 1 dose-escalation study of IV ixazomib, an investigational proteasome 
      inhibitor, in patients with relapsed/refractory lymphoma.
PG  - e251
LID - 10.1038/bcj.2014.71 [doi]
AB  - Ixazomib is an investigational proteasome inhibitor that has shown preclinical 
      activity in lymphoma models. This phase 1 study assessed the safety, 
      tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics 
      and preliminary activity of intravenous (IV) ixazomib in relapsed/refractory 
      lymphoma patients who had received ⩾ 2 prior therapies. Thirty patients with a 
      range of histologies received ixazomib 0.125-3.11 mg/m(2) on days 1, 8 and 15 of 
      28-day cycles. Patients received a median of two cycles (range 1-36). MTD was 
      determined to be 2.34 mg/m(2). Most common drug-related adverse events (AEs) 
      included fatigue (43%), diarrhea (33%), nausea, vomiting and thrombocytopenia 
      (each 27%). Drug-related grade ⩾ 3 AEs included neutropenia (20%), 
      thrombocytopenia (13%) and diarrhea (10%). Drug-related peripheral neuropathy 
      occurred in four (13%) patients; no grade ⩾ 3 events were reported. Plasma 
      exposure increased dose proportionally from 0.5-3.11 mg/m(2); terminal half-life 
      was 4-12 days after multiple dosing. Of 26 evaluable patients, five achieved 
      responses: 4/11 follicular lymphoma patients (one complete and three partial 
      responses) and 1/4 peripheral T-cell lymphoma patients (partial response). 
      Sustained responses were observed with ⩾ 32 cycles of treatment in two heavily 
      pretreated follicular lymphoma patients. Results suggest weekly IV ixazomib is 
      generally well tolerated and may be clinically active in relapsed/refractory 
      lymphoma.
FAU - Assouline, S E
AU  - Assouline SE
AD  - Department of Oncology, Jewish General Hospital, McGill University, Montreal, 
      Quebec, Canada.
FAU - Chang, J
AU  - Chang J
AD  - Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI, USA.
FAU - Cheson, B D
AU  - Cheson BD
AD  - Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, 
      DC, USA.
FAU - Rifkin, R
AU  - Rifkin R
AD  - Rocky Mountain Cancer Center, Denver, CO, USA.
FAU - Hamburg, S
AU  - Hamburg S
AD  - Tower Cancer Research Foundation, Beverly Hills, CA, USA.
FAU - Reyes, R
AU  - Reyes R
AD  - University of Kansas Medical Center, Kansas City, KS, USA.
FAU - Hui, A-M
AU  - Hui AM
AD  - Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
FAU - Yu, J
AU  - Yu J
AD  - Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
FAU - Gupta, N
AU  - Gupta N
AD  - Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
FAU - Di Bacco, A
AU  - Di Bacco A
AD  - Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
FAU - Shou, Y
AU  - Shou Y
AD  - Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
FAU - Martin, P
AU  - Martin P
AD  - Weill Cornell Medical College, New York, NY, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20141017
PL  - United States
TA  - Blood Cancer J
JT  - Blood cancer journal
JID - 101568469
RN  - 0 (Boron Compounds)
RN  - 0 (Proteasome Inhibitors)
RN  - 71050168A2 (ixazomib)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Boron Compounds/*administration & dosage/adverse effects
MH  - Diarrhea/chemically induced/epidemiology
MH  - Female
MH  - Glycine/administration & dosage/adverse effects/*analogs & derivatives
MH  - Humans
MH  - Lymphoma, Follicular/*drug therapy/epidemiology
MH  - Lymphoma, T-Cell, Peripheral/*drug therapy/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Neutropenia/chemically induced/epidemiology
MH  - Peripheral Nervous System Diseases/chemically induced/epidemiology
MH  - Proteasome Inhibitors/*administration & dosage/adverse effects
MH  - Thrombocytopenia/chemically induced/epidemiology
PMC - PMC4220649
EDAT- 2014/10/18 06:00
MHDA- 2015/09/17 06:00
PMCR- 2014/10/01
CRDT- 2014/10/18 06:00
PHST- 2014/09/01 00:00 [received]
PHST- 2014/09/02 00:00 [accepted]
PHST- 2014/10/18 06:00 [entrez]
PHST- 2014/10/18 06:00 [pubmed]
PHST- 2015/09/17 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - bcj201471 [pii]
AID - 10.1038/bcj.2014.71 [doi]
PST - epublish
SO  - Blood Cancer J. 2014 Oct 17;4(10):e251. doi: 10.1038/bcj.2014.71.