PMID- 24919462
OWN - NLM
STAT- MEDLINE
DCOM- 20140926
LR  - 20211021
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 7
DP  - 2014 Jun 12
TI  - A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large 
      B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors.
PG  - 44
LID - 10.1186/1756-8722-7-44 [doi]
AB  - BACKGROUND: Patients with DLBCL who are ineligible for or have relapsed after 
      aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on 
      multiple B-cell neoplasms including DLBCL and is a potential target for 
      immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized 
      IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma 
      activity in a phase I study. METHODS: A phase II study was undertaken to evaluate 
      the rate and duration of objective responses and safety of single-agent 
      dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory 
      DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient 
      dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, 
      followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and 
      duration of objective responses, safety, survival, pharmacokinetics, 
      immunogenicity, and exploratory correlative studies. RESULTS: Overall response 
      rate was 9% and disease control rate (complete remission + partial 
      remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) 
      included fatigue, headache, chills, fever, and nausea. The most frequent Grade 
      3-4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3-4 
      lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without 
      associated infection or bleeding. Reversible ocular events, including 
      conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). 
      Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear 
      to correlate with antitumor activity. CONCLUSIONS: Single-agent dacetuzumab has 
      modest activity and manageable toxicity in unselected patients with relapsed 
      DLBCL. Combination regimens and robust methods of patient selection may be 
      necessary for further development. TRIAL REGISTRATION: ClinicalTrials.gov 
      identifier NCT00435916.
FAU - de Vos, Sven
AU  - de Vos S
AD  - David Geffen School of Medicine at UCLA, University of California Los Angeles, 
      650 Charles E, Young Drive 11-934 Factor Bldg, Los Angeles, CA 90095-1678, USA. 
      deVos@mednet.ucla.edu.
FAU - Forero-Torres, Andres
AU  - Forero-Torres A
FAU - Ansell, Stephen M
AU  - Ansell SM
FAU - Kahl, Brad
AU  - Kahl B
FAU - Cheson, Bruce D
AU  - Cheson BD
FAU - Bartlett, Nancy L
AU  - Bartlett NL
FAU - Furman, Richard R
AU  - Furman RR
FAU - Winter, Jane N
AU  - Winter JN
FAU - Kaplan, Henry
AU  - Kaplan H
FAU - Timmerman, John
AU  - Timmerman J
FAU - Whiting, Nancy C
AU  - Whiting NC
FAU - Drachman, Jonathan G
AU  - Drachman JG
FAU - Advani, Ranjana
AU  - Advani R
LA  - eng
SI  - ClinicalTrials.gov/NCT00435916
GR  - P30 CA014520/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140612
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (CD40 Antigens)
RN  - 0 (FCGR3A protein, human)
RN  - 0 (Fc gamma receptor IIA)
RN  - 0 (Receptors, IgG)
RN  - UT59FF4T5X (dacetuzumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/adverse effects/pharmacokinetics/*therapeutic 
      use
MH  - CD40 Antigens/immunology/metabolism
MH  - Chills/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Fatigue/chemically induced
MH  - Female
MH  - Headache/chemically induced
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lymphoma, Large B-Cell, Diffuse/*drug therapy/pathology
MH  - Lymphopenia/chemically induced
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, IgG/genetics
MH  - Remission Induction
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4065310
EDAT- 2014/06/13 06:00
MHDA- 2014/09/27 06:00
PMCR- 2014/06/12
CRDT- 2014/06/13 06:00
PHST- 2014/03/21 00:00 [received]
PHST- 2014/05/21 00:00 [accepted]
PHST- 2014/06/13 06:00 [entrez]
PHST- 2014/06/13 06:00 [pubmed]
PHST- 2014/09/27 06:00 [medline]
PHST- 2014/06/12 00:00 [pmc-release]
AID - 1756-8722-7-44 [pii]
AID - 10.1186/1756-8722-7-44 [doi]
PST - epublish
SO  - J Hematol Oncol. 2014 Jun 12;7:44. doi: 10.1186/1756-8722-7-44.