PMID- 32040960
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20230916
IS  - 1539-3704 (Electronic)
IS  - 0003-4819 (Print)
IS  - 0003-4819 (Linking)
VI  - 172
IP  - 5
DP  - 2020 Mar 3
TI  - Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in 
      Transplant Recipients: A Phase 2, Randomized Clinical Trial.
PG  - 306-316
LID - 10.7326/M19-2511 [doi]
AB  - BACKGROUND: Triplex vaccine was developed to enhance cytomegalovirus 
      (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic 
      stem cell transplant (HCT). OBJECTIVE: To determine the safety and efficacy of 
      Triplex. DESIGN: First-in-patient, phase 2 trial. (ClinicalTrials.gov: 
      NCT02506933). SETTING: 3 U.S. HCT centers. PARTICIPANTS: 102 CMV-seropositive HCT 
      recipients at high risk for CMV reactivation. INTERVENTION: Intramuscular 
      injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex 
      is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing 
      immunodominant CMV antigens. MEASUREMENTS: The primary outcomes were CMV events 
      (CMV DNA level >/=1250 IU/mL, CMV viremia requiring antiviral treatment, or 
      end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) 
      graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and 
      grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were 
      probably or definitely attributable to injection. RESULTS: A total of 102 
      patients (51 per group) received the first vaccination, and 91 (89.2%) received 
      both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 
      Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 
      0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during 
      the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to 
      vaccination were observed within 2 weeks after vaccination. Incidence of severe 
      acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 
      0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with 
      effector memory phenotype were significantly higher in Triplex than placebo 
      recipients. LIMITATION: The lower-than-expected incidence of CMV events in the 
      placebo group reduced the power of the trial. CONCLUSION: No vaccine-associated 
      safety concerns were identified. Triplex elicited and amplified CMV-specific 
      immune responses, and fewer Triplex-vaccinated patients had CMV viremia. PRIMARY 
      FUNDING SOURCE: National Cancer Institute and Helocyte.
FAU - Aldoss, Ibrahim
AU  - Aldoss I
AD  - City of Hope Comprehensive Cancer Center, Duarte, California (I.A., L.F., A.N., 
      M.M.A., R.N.).
FAU - La Rosa, Corinna
AU  - La Rosa C
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Baden, Lindsey R
AU  - Baden LR
AD  - Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, 
      Massachusetts (L.R.B., N.C.I.).
FAU - Longmate, Jeffrey
AU  - Longmate J
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Ariza-Heredia, Ella J
AU  - Ariza-Heredia EJ
AD  - The University of Texas MD Anderson Cancer Center, Houston, Texas (E.J.A.).
FAU - Rida, Wasima N
AU  - Rida WN
AD  - Biostatistics Consultant, Arlington, Virginia (W.N.R.).
FAU - Lingaraju, Chetan Raj
AU  - Lingaraju CR
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Zhou, Qiao
AU  - Zhou Q
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Martinez, Joy
AU  - Martinez J
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Kaltcheva, Teodora
AU  - Kaltcheva T
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Dagis, Andy
AU  - Dagis A
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Hardwick, Nicola
AU  - Hardwick N
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Issa, Nicolas C
AU  - Issa NC
AD  - Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, 
      Massachusetts (L.R.B., N.C.I.).
FAU - Farol, Len
AU  - Farol L
AD  - City of Hope Comprehensive Cancer Center, Duarte, California (I.A., L.F., A.N., 
      M.M.A., R.N.).
FAU - Nademanee, Auayporn
AU  - Nademanee A
AD  - City of Hope Comprehensive Cancer Center, Duarte, California (I.A., L.F., A.N., 
      M.M.A., R.N.).
FAU - Al Malki, Monzr M
AU  - Al Malki MM
AD  - City of Hope Comprehensive Cancer Center, Duarte, California (I.A., L.F., A.N., 
      M.M.A., R.N.).
FAU - Forman, Stephen
AU  - Forman S
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
FAU - Nakamura, Ryotaro
AU  - Nakamura R
AD  - City of Hope Comprehensive Cancer Center, Duarte, California (I.A., L.F., A.N., 
      M.M.A., R.N.).
FAU - Diamond, Don J
AU  - Diamond DJ
AD  - City of Hope Comprehensive Cancer Center and the Beckman Research Institute of 
      City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., 
      N.H., S.F., D.J.D.).
CN  - TRIPLEX VACCINE Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT02506933
GR  - P30 CA033572/CA/NCI NIH HHS/United States
GR  - R01 CA077544/CA/NCI NIH HHS/United States
GR  - R01 CA181045/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200211
PL  - United States
TA  - Ann Intern Med
JT  - Annals of internal medicine
JID - 0372351
RN  - 0 (Cytomegalovirus Vaccines)
SB  - IM
MH  - Aged
MH  - *Cytomegalovirus/immunology
MH  - Cytomegalovirus Infections/*prevention & control
MH  - Cytomegalovirus Vaccines/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Hematopoietic Stem Cell Transplantation/*adverse effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Viremia/*prevention & control
PMC - PMC9074089
MID - NIHMS1799505
FIR - Baden, Lindsey R
IR  - Baden LR
FIR - Issa, Nicholas C
IR  - Issa NC
FIR - Aldoss, Ibrahim
IR  - Aldoss I
FIR - Al Malki, Monzr M
IR  - Al Malki MM
FIR - Diamond, Don J
IR  - Diamond DJ
FIR - Farol, Len J
IR  - Farol LJ
FIR - Forman, Stephen
IR  - Forman S
FIR - Hardwick, Nicola
IR  - Hardwick N
FIR - Kaltcheva, Teodora
IR  - Kaltcheva T
FIR - La Rosa, Corinna
IR  - La Rosa C
FIR - Lingaraju, Chetan Raj
IR  - Lingaraju CR
FIR - Martinez, Joy
IR  - Martinez J
FIR - Nademanee, Auayporn
IR  - Nademanee A
FIR - Nakamura, Ryotaro
IR  - Nakamura R
FIR - Zhou, Qiao
IR  - Zhou Q
FIR - Dagis, Andy
IR  - Dagis A
FIR - Longmate, Jeffrey
IR  - Longmate J
FIR - Rida, Wasima N
IR  - Rida WN
FIR - Ariza-Heredia, Ella J
IR  - Ariza-Heredia EJ
FIR - Haddad, Esther Arbona
IR  - Haddad EA
FIR - Pandit, Alisha
IR  - Pandit A
FIR - Drake, Jennifer
IR  - Drake J
FIR - Duarte, Lupe
IR  - Duarte L
FIR - Morrison, Thomas
IR  - Morrison T
FIR - Paris, Tania
IR  - Paris T
FIR - Slape, Cynthia
IR  - Slape C
FIR - Palmer, Joycelynne
IR  - Palmer J
FIR - Araujo, Gloria
IR  - Araujo G
FIR - Lobo, Yadira
IR  - Lobo Y
EDAT- 2020/02/11 06:00
MHDA- 2020/09/01 06:00
PMCR- 2022/05/06
CRDT- 2020/02/11 06:00
PHST- 2020/02/11 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2020/02/11 06:00 [entrez]
PHST- 2022/05/06 00:00 [pmc-release]
AID - 2760880 [pii]
AID - 10.7326/M19-2511 [doi]
PST - ppublish
SO  - Ann Intern Med. 2020 Mar 3;172(5):306-316. doi: 10.7326/M19-2511. Epub 2020 Feb 
      11.