PMID- 24615778
OWN - NLM
STAT- MEDLINE
DCOM- 20140731
LR  - 20231120
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 123
IP  - 22
DP  - 2014 May 29
TI  - A phase 1 study of the PI3Kdelta inhibitor idelalisib in patients with 
      relapsed/refractory mantle cell lymphoma (MCL).
PG  - 3398-405
LID - 10.1182/blood-2013-11-537555 [doi]
AB  - Idelalisib, an oral inhibitor of phosphatidylinositol-3-kinase delta (PI3Kdelta), was 
      evaluated in a 48-week phase 1 study (50-350 mg daily or twice daily) enrolling 
      40 patients with relapsed or refractory mantle cell lymphoma (MCL). Primary 
      outcome was safety and dose-limiting toxicity (DLT). Secondary outcomes were 
      pharmacokinetic parameters, pharmacodynamic effects, overall response rate (ORR), 
      progression-free survival (PFS), and duration of response (DOR). Patients without 
      DLT and no evidence of disease progression after 48 weeks enrolled in the 
      extension study. Patients had median age of 69 years (range, 52-83) and received 
      median of 4 prior therapies (1-14); 17 of 40 patients (43%) were refractory to 
      their most recent treatment. Median duration of idelalisib treatment was 3.5 
      months (range, 0.7-30.7), with 6 (15%) continuing extension treatment. Common 
      grade >/=3 adverse events (AEs) included (total%/grade >/=3%) diarrhea (40/18), 
      nausea (33/5), pyrexia (28/0), fatigue (25/3), rash (23/3), decreased appetite 
      (20/15), upper respiratory infection (20/0), pneumonia (13/10), and alanine 
      transaminase or aspartate transaminase elevations (60/20). ORR was 16 of 40 
      patients (40%), with CR in 2 of 40 patients (5%). Median DOR was 2.7 months, 
      median PFS was 3.7 months, and 1-year PFS was 22%. These data provide proof of 
      concept that targeting PI3Kdelta is a viable strategy and worthy of additional study 
      in MCL. This trial was registered at www.clinicaltrials.gov as #NCT00710528.
CI  - (c) 2014 by The American Society of Hematology.
FAU - Kahl, Brad S
AU  - Kahl BS
AD  - Department of Medicine, University of Wisconsin Carbone Cancer Center, Madison, 
      WI;
FAU - Spurgeon, Stephen E
AU  - Spurgeon SE
AD  - Department of Medicine, Oregon Health and Sciences University, Portland, OR;
FAU - Furman, Richard R
AU  - Furman RR
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY;
FAU - Flinn, Ian W
AU  - Flinn IW
AD  - Sarah Cannon Research Institute, Nashville, TN;
FAU - Coutre, Steven E
AU  - Coutre SE
AD  - Stanford University Medical Center, Stanford, CA;
FAU - Brown, Jennifer R
AU  - Brown JR
AD  - Dana-Farber Cancer Institute, Boston, MA;
FAU - Benson, Don M
AU  - Benson DM
AD  - Department of Medicine, Ohio State University, Columbus, OH;
FAU - Byrd, John C
AU  - Byrd JC
AD  - Department of Medicine, Ohio State University, Columbus, OH;
FAU - Peterman, Sissy
AU  - Peterman S
AD  - Gilead Sciences, Seattle, WA; and.
FAU - Cho, Yoonjin
AU  - Cho Y
AD  - Gilead Sciences, Seattle, WA; and.
FAU - Yu, Albert
AU  - Yu A
AD  - Gilead Sciences, Seattle, WA; and.
FAU - Godfrey, Wayne R
AU  - Godfrey WR
AD  - Gilead Sciences, Seattle, WA; and.
FAU - Wagner-Johnston, Nina D
AU  - Wagner-Johnston ND
AD  - Department of Medicine, Washington University School of Medicine, St. Louis, MO.
LA  - eng
SI  - ClinicalTrials.gov/NCT00710528
GR  - P30 CA014520/CA/NCI NIH HHS/United States
GR  - UL1 TR000427/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140310
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Purines)
RN  - 0 (Quinazolinones)
RN  - YG57I8T5M0 (idelalisib)
SB  - IM
CIN - Blood. 2014 May 29;123(22):3368-70. PMID: 24876522
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Lymphoma, Mantle-Cell/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Purines/pharmacology/*therapeutic use
MH  - Quinazolinones/pharmacology/*therapeutic use
MH  - Recurrence
MH  - Risk Factors
MH  - Treatment Outcome
PMC - PMC4260977
EDAT- 2014/03/13 06:00
MHDA- 2014/08/01 06:00
PMCR- 2015/05/29
CRDT- 2014/03/12 06:00
PHST- 2014/03/12 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2014/08/01 06:00 [medline]
PHST- 2015/05/29 00:00 [pmc-release]
AID - S0006-4971(20)35595-6 [pii]
AID - 2013/537555 [pii]
AID - 10.1182/blood-2013-11-537555 [doi]
PST - ppublish
SO  - Blood. 2014 May 29;123(22):3398-405. doi: 10.1182/blood-2013-11-537555. Epub 2014 
      Mar 10.