Evidence map›Paper›PMID 30824040›Full record

Trial reportThe Lancet. Haematology2019

Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomised phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203).

Javier Bolaños-Meade, Ran Reshef, Raphael Fraser, Mingwei Fei, Sunil Abhyankar, Zaid Al-Kadhimi, Amin M Alousi, Joseph H Antin, Sally Arai, Kate Bickett and 24 more

Abstract readClinical Trial, Phase IIComparative StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Haematology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed, 3 pooled it
23.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

165 citing papers in PubMed, 3 syntheses or guidelines pooled it, 277 citations in OpenAlex.

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  20. Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020
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105 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 20 institutions in 1 country.

Javier Bolaños-MeadeDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. Electronic address: fbolano2@jhmi.edu.
Ran ReshefDepartment of Medicine, Columbia University Medical Center, New York, NY, USA.
Raphael FraserDepartment of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
Mingwei FeiDepartment of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
Sunil AbhyankarDepartment of Internal Medicine, University of Kansas Medical Center, Westwood, KS, USA.
Zaid Al-KadhimiDepartment of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Amin M AlousiDepartment of Stem Cell Transplant and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joseph H AntinDepartment of Medicial Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sally AraiDepartment of Medicine, Stanford University, Palo Alto, CA, USA.
Kate BickettThe Emmes Corporation, Rockville, MD, USA.
Yi-Bin ChenDepartment of Medicine, Massachusetts General, Hospital, Boston, MA, USA.
Lloyd E DamonDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Yvonne A EfeberaDepartment of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Nancy L GellerOffice of Biostatistics Research, National Institutes of Health, Bethesda, MD, USA.
Sergio A GiraltDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Parameswaran HariDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Shernan G HoltanDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.
Mary M HorowitzDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
David A JacobsohnDepartment of Pediatrics at George Washington University, Children's National Medical Center, Washington, DC, USA.
Richard J JonesDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Jane L LiesveldDepartment of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Brent R LoganDepartment of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
Margaret L MacMillanDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Marco MielcarekClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Pierre NoelDepartment of Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA.
Joseph PidalaBlood and Marrow Transplantation and Cellular Immunotherapy, H Lee Moffitt Cancer Center, Tampa, FL, USA.
David L PorterDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Iskra PusicDepartment of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
Ronald SobecksDepartment of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA.
Scott R SolomonBlood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
Daniel J WeisdorfDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.
Juan WuThe Emmes Corporation, Rockville, MD, USA.
Marcelo C PasquiniDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
John KorethDepartment of Medicial Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Medical College of Wisconsin · USUniversity of Minnesota · USDana-Farber Cancer Institute · USEmmes (United States) · USChildren's National · USCleveland Clinic · USColumbia University Irving Medical Center · USEmory University · USFred Hutch Cancer Center · USJohns Hopkins University · USMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · USMoffitt Cancer Center · USNational Institutes of Health · USNorthside Hospital · USSidney Kimmel Comprehensive Cancer Center · USStanford University · USThe Ohio State University · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, San Francisco · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Data Resource for Analyzing Blood &Marrow TransplantsU24CA076518 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI Amy M Moskop, Bronwen Shaw · 1998 to 2026
$105.2M
TUMOR SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN BONE MARROW TRANSPLANTATIONP01CA049605 · NCI · STANFORD UNIVERSITY · PI David B. Miklos · 1989 to 2026
$73.3M
Blood and Marrow Transplant Clinical Trials Network DCC- The Medical College of Wisconsin, Inc.U24HL138660 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Steven M. DeVine, Mehdi Hussain Hamadani · 2017 to 2026
$71.4M
Easy-to-read Informed Consent for HCT Clinical TrialsU10HL069294 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI HOROWITZ, MARY MARESCA · 2011 to 2016
$43.8M
MSKCC BMT CTN RenewalUG1HL069315 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI MIGUEL-ANGEL PERALES · 2017 to 2026
$2.2M
BMT CTN Core - Dana-Farber Cancer Institute and MGH ConsortiumUG1HL069249 · NHLBI · DANA-FARBER CANCER INST · PI Mahasweta Gooptu · 2017 to 2026
$2.2M
Targeting HIV and EBV Antigens in Patients with HIV LymphomaUG1HL108945 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Catherine M. Bollard, HELEN E HESLOP · 2017 to 2026
$2.1M
BMT CTN Core - University of MinnesotaUG1HL069290 · NHLBI · UNIVERSITY OF MINNESOTA · PI Mark Juckett, Margaret L MacMillan · 2017 to 2026
$1.9M
Phase III, Multicenter, Randomized, Double-Blind Study of Duvelisib as Cytokine Release Syndrome Prophylaxis in Patients with Large Cell or Mantle Cell Lymphoma Undergoing CAR T-Cell TherapiesUG1HL109137 · NHLBI · WASHINGTON UNIVERSITY · PI Iskra Pusic · 2017 to 2026
$1.9M
BMT Core - Stanford UniversityUG1HL069291 · NHLBI · STANFORD UNIVERSITY · PI Lori Muffly · 2017 to 2026
$1.7M
Translational Research in Blood and Marrow TransplantationUG1HL069310 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI RICHARD J JONES · 2017 to 2026
$1.6M
NCI NIH HHS P01 CA049605NCI NIH HHS P30 CA008748NCI NIH HHS U24 CA076518NHLBI NIH HHS U10 HL069291NHLBI NIH HHS U10 HL069294NHLBI NIH HHS U24 HL138660NHLBI NIH HHS UG1 HL069249NHLBI NIH HHS UG1 HL069290NHLBI NIH HHS UG1 HL069291NHLBI NIH HHS UG1 HL069310NHLBI NIH HHS UG1 HL069315NHLBI NIH HHS UG1 HL108945NHLBI NIH HHS UG1 HL109137
6 · The paper itself

Abstract

backgroundPrevention of graft-versus-host disease (GvHD) without malignant relapse is the overall goal of allogeneic haemopoietic cell transplantation (HCT). We aimed to evaluate regimens using either maraviroc, bortezomib, or post-transplantation cyclophosphamide for GvHD prophylaxis compared with controls receiving the combination of tacrolimus and methotrexate using a novel composite primary endpoint to identify the most promising intervention to be further tested in a phase 3 trial.

methodsIn this prospective multicentre phase 2 trial, adult patients aged 18-75 years who received reduced-intensity conditioning HCT were randomly assigned (1:1:1) by random block sizes to tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide (cyclophosphamide 50 mg/kg on days 3 and 4, followed by tacrolimus starting on day 5 and mycophenolate mofetil starting on day 5 at 15 mg/kg three times daily not to exceed 1 g from day 5 to day 35); tacrolimus, methotrexate, and bortezomib (bortezomib 1·3 mg/m

findingsBetween Nov 17, 2014, and May 18, 2016, 273 patients from 31 US centres were randomly assigned to the three study arms: 89 to tacrolimus, methotrexate, and bortezomib; 92 to tacrolimus, methotrexate, and maraviroc; 92 to tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; and six were excluded. Between Aug 1, 2014, and Sept 14, 2016, 224 controls received tacrolimus and methotrexate. Controls were generally well matched except for more frequent comorbidities than the intervention groups and a different distribution of types of conditioning regimens used. Compared with controls, the hazard ratio for GRFS was 0·72 (90% CI 0·54-0·94; p=0·044) for tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide, 0·98 (0·76-1·27; p=0·92) for tacrolimus, methotrexate, and bortezomib, and 1·10 (0·86-1·41; p=0·49) for tacrolimus, methotrexate, and maraviroc. 238 patients experienced grade 3 or 4 toxicities: 12 (13%) had grade 3 and 67 (73%) grade 4 events with tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; ten (11%) had grade 3 and 68 (76%) had grade 4 events with tacrolimus, methotrexate, and bortezomib; and 18 (20%) had grade 3 and 63 (68%) had grade 4 events with tacrolimus, methotrexate, and maraviroc. The most common toxicities were haematological (77 [84%] for tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; 73 [82%] for tacrolimus, methotrexate, and bortezomib; and 78 [85%] for tacrolimus, methotrexate, and maraviroc) and cardiac (43 [47%], 44 [49%], and 43 [47%], respectively).

interpretationTacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide was the most promising intervention, yielding the best GRFS; this regimen is thus being prospectively compared with tacrolimus and methotrexate in a phase 3 randomised trial.

fundingUS National Health, Lung, and Blood Institute; National Cancer Institute; National Institute of Allergy and Infectious Disease; and Millennium Pharmaceuticals.

Indexed as

Transplantation ConditioningAgedBortezomibCyclophosphamideDrug InteractionsFemaleGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansMaleMaravirocMethotrexateMiddle AgedMycophenolic AcidTacrolimusBortezomibCyclophosphamideMaravirocMethotrexateMycophenolic AcidTacrolimus

Identifiers

PMID30824040
PMCPMC6503965
OpenAlexW2917040403

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.