PMID- 28683766
OWN - NLM
STAT- MEDLINE
DCOM- 20180103
LR  - 20220321
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 10
IP  - 1
DP  - 2017 Jul 6
TI  - Randomized, double-blind, placebo-controlled phase III study of ixazomib plus 
      lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma: 
      China Continuation study.
PG  - 137
LID - 10.1186/s13045-017-0501-4 [doi]
LID - 137
AB  - BACKGROUND: The China Continuation study was a separate regional expansion of the 
      global, double-blind, placebo-controlled, randomized phase III TOURMALINE-MM1 
      study of ixazomib plus lenalidomide-dexamethasone (Rd) in patients with 
      relapsed/refractory multiple myeloma (RRMM) following one to three prior 
      therapies. METHODS: Patients were randomized (1:1) to receive ixazomib 4.0 mg or 
      placebo on days 1, 8, and 15, plus lenalidomide 25 mg on days 1-21 and 
      dexamethasone 40 mg on days 1, 8, 15, and 22, in 28-day cycles. Randomization was 
      stratified according to number of prior therapies, disease stage, and prior 
      proteasome inhibitor exposure. The primary endpoint was progression-free survival 
      (PFS). In total, 115 Chinese patients were randomized (57 ixazomib-Rd, 58 
      placebo-Rd). RESULTS: At the preplanned final analysis for PFS, after median PFS 
      follow-up of 7.4 and 6.9 months, respectively, PFS was improved with ixazomib-Rd 
      versus placebo-Rd (median 6.7 vs 4.0 months; HR 0.598; p = 0.035). At the 
      preplanned final analysis of overall survival (OS), after median follow-up of 
      20.2 and 19.1 months, respectively, OS was improved with ixazomib-Rd versus 
      placebo-Rd (median 25.8 vs 15.8 months; HR 0.419; p = 0.001). On the ixazomib-Rd 
      and placebo-Rd arms, respectively, 38 (67%) and 43 (74%) patients reported grade 
      >/=3 adverse events (AEs), 19 (33%) and 18 (31%) reported serious AEs, and 4 (7%) 
      and 5 (9%) died on-study. The most frequent grade 3/4 AEs were thrombocytopenia 
      (18%/7% vs 14%/5%), neutropenia (19%/5% vs 19%/2%), and anemia (12%/0 vs 26%/2%). 
      CONCLUSIONS: This study demonstrated that PFS and OS were significantly improved 
      with ixazomib-Rd versus placebo-Rd, with limited additional toxicity, in patients 
      with RRMM. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01564537.
FAU - Hou, Jian
AU  - Hou J
AD  - Department of Hematology, Chang Zheng Hospital, The Second Military Medical 
      University, Shanghai, 200003, China. houjian167@sohu.com.
FAU - Jin, Jie
AU  - Jin J
AD  - First Hospital Affiliated Zhe Jiang Medical University, Hangzhou, China.
FAU - Xu, Yan
AU  - Xu Y
AD  - Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical 
      Science & Peking Union Medical College, Tianjin, China.
FAU - Wu, Depei
AU  - Wu D
AD  - The First Affiliated Hospital of Soochow University, Jiangsu, China.
FAU - Ke, Xiaoyan
AU  - Ke X
AD  - The Third Affiliated Hospital of Beijing Medical University, Beijing, China.
FAU - Zhou, Daobin
AU  - Zhou D
AD  - Peking Union Medical College Hospital, Beijing, China.
FAU - Lu, Jin
AU  - Lu J
AD  - Peking University People's Hospital, Beijing, China.
FAU - Du, Xin
AU  - Du X
AD  - Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou, 
      China.
FAU - Chen, Xiequn
AU  - Chen X
AD  - Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
FAU - Li, Junmin
AU  - Li J
AD  - Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.
FAU - Liu, Jing
AU  - Liu J
AD  - The Third Hospital Xiang Ya Medical University, Changsha, China.
FAU - Gupta, Neeraj
AU  - Gupta N
AD  - Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited.), Cambridge, MA, USA.
FAU - Hanley, Michael J
AU  - Hanley MJ
AD  - Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited.), Cambridge, MA, USA.
FAU - Li, Hongmei
AU  - Li H
AD  - Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited.), Cambridge, MA, USA.
FAU - Hua, Zhaowei
AU  - Hua Z
AD  - Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited.), Cambridge, MA, USA.
FAU - Wang, Bingxia
AU  - Wang B
AD  - Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited.), Cambridge, MA, USA.
FAU - Zhang, Xiaoquan
AU  - Zhang X
AD  - Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited.), Cambridge, MA, USA.
FAU - Wang, Hui
AU  - Wang H
AD  - Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited.), Cambridge, MA, USA.
FAU - van de Velde, Helgi
AU  - van de Velde H
AD  - Millennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited.), Cambridge, MA, USA.
FAU - Richardson, Paul G
AU  - Richardson PG
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Moreau, Philippe
AU  - Moreau P
AD  - University Hospital Hotel-Dieu, Nantes, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT01564537
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170706
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Boron Compounds)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 71050168A2 (ixazomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - F0P408N6V4 (Lenalidomide)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Boron Compounds/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - China/epidemiology
MH  - Dexamethasone/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Disease-Free Survival
MH  - Double-Blind Method
MH  - Female
MH  - Glycine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics/therapeutic use
MH  - Humans
MH  - Lenalidomide
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/epidemiology
MH  - Neoplasm Recurrence, Local/*drug therapy
MH  - Placebo Effect
MH  - Thalidomide/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics/therapeutic use
PMC - PMC5500972
OTO - NOTNLM
OT  - China
OT  - Ixazomib
OT  - Multiple myeloma
OT  - Oral
OT  - Overall survival
OT  - Progression-free survival
OT  - Proteasome inhibitor
OT  - Relapsed/refractory
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Details of all sites' ethics 
      committee approvals are provided in Additional file 3. All patients provided 
      written informed consent. CONSENT FOR PUBLICATION: Not applicable. COMPETING 
      INTERESTS: NG, MJH, HL, ZH, BW, XZ, HW, HvdV: employment, Millennium 
      Pharmaceuticals, Inc., Cambridge, MA, USA a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited. PGR: consultancy/advisory role for 
      Millennium/Takeda and Celgene. PM: advisory boards for Takeda, Celgene, Janssen, 
      Amgen, and Novartis. JH, JJ, YX, DW, XK, ZD, JLu, XD, XC, JLi, JLiu: no conflicts 
      of interest disclosed. PUBLISHER'S NOTE: Springer Nature remains neutral with 
      regard to jurisdictional claims in published maps and institutional affiliations.
EDAT- 2017/07/08 06:00
MHDA- 2018/01/04 06:00
PMCR- 2017/07/06
CRDT- 2017/07/08 06:00
PHST- 2017/05/02 00:00 [received]
PHST- 2017/06/26 00:00 [accepted]
PHST- 2017/07/08 06:00 [entrez]
PHST- 2017/07/08 06:00 [pubmed]
PHST- 2018/01/04 06:00 [medline]
PHST- 2017/07/06 00:00 [pmc-release]
AID - 10.1186/s13045-017-0501-4 [pii]
AID - 501 [pii]
AID - 10.1186/s13045-017-0501-4 [doi]
PST - epublish
SO  - J Hematol Oncol. 2017 Jul 6;10(1):137. doi: 10.1186/s13045-017-0501-4.