Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas.
A phase 1 study with carfilzomib and vorinostat was conducted in 20 B-cell lymphoma patients. Vorinostat was given orally twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 followed by carfilzomib (given as a 30-min infusion) on days 1, 2, 8, 9, 15, and 16. A treatment cycle was 28 days. Dose escalation initially followed a standard 3 + 3 design, but adapted a more conservative accrual rule following dose de-escalation. The maximum tolerated dose was 20 mg/m2 carfilzomib and 100 mg vorinostat (twice daily). The dose-limiting toxicities were grade 3 pneumonitis, hyponatremia, and febrile neutropenia. One patient had a partial response and two patients had stable disease. Correlative studies showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response.
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .|b Department of Internal Medicine , Virginia Commonwealth University , Richmond , VA , USA .
Beata
B
Holkova
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .
Maciej
M
Kmieciak
c University of Texas MD Anderson Cancer Center , Houston , TX , USA .
Prithviraj
P
Bose
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .|b Department of Internal Medicine , Virginia Commonwealth University , Richmond , VA , USA .
Victor Y
VY
Yazbeck
d James P. Wilmot Cancer Center, University of Rochester , Rochester , NY , USA .
Paul M
PM
Barr
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .
Mary Beth
MB
Tombes
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .
Ellen
E
Shrader
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .
Caryn
C
Weir-Wiggins
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .
April D
AD
Rollins
d James P. Wilmot Cancer Center, University of Rochester , Rochester , NY , USA .
Erin M
EM
Cebula
d James P. Wilmot Cancer Center, University of Rochester , Rochester , NY , USA .
Emily
E
Pierce
d James P. Wilmot Cancer Center, University of Rochester , Rochester , NY , USA .
Megan
M
Herr
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .
Heidi
H
Sankala
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .
Kevin T
KT
Hogan
e Department of Biostatistics , Virginia Commonwealth University , Richmond , VA , USA .
Wen
W
Wan
d James P. Wilmot Cancer Center, University of Rochester , Rochester , NY , USA .|f Department of Biostatistics and Computational Biology , University of Rochester , Rochester , NY , USA .
Changyong
C
Feng
f Department of Biostatistics and Computational Biology , University of Rochester , Rochester , NY , USA .
Derick R
DR
Peterson
g Fox Chase Cancer Center , Temple Health , Philadelphia , PA , USA .
Richard I
RI
Fisher
a Massey Cancer Center and Virginia Commonwealth University , Richmond , VA , USA .|b Department of Internal Medicine , Virginia Commonwealth University , Richmond , VA , USA .|h Department of Microbiology and Immunology , Virginia Commonwealth University , Richmond , VA , USA .|i Department of Biochemistry and Molecular Biology , Virginia Commonwealth University , Richmond , VA , USA .|j The Institute for Molecular Medicine , Virginia Commonwealth University , Richmond , VA , USA , and.
Steven
S
Grant
d James P. Wilmot Cancer Center, University of Rochester , Rochester , NY , USA .|k Department of Medicine , University of Rochester , Rochester, NY , USA.
Jonathan W
JW
Friedberg
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D016903:Drug Monitoring; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D016393:Lymphoma, B-Cell / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009842:Oligopeptides / Q000008:administration & dosage; D019233:Retreatment; D016896:Treatment Outcome; D000077337:Vorinostat
D015415:Biomarkers; D016207:Cytokines; D006877:Hydroxamic Acids; D009842:Oligopeptides; D000077337:Vorinostat; C524865:carfilzomib
Carfilzomib; lymphoma; phase 1 clinical trial; vorinostat