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NCT03657160

Vedolizumab in the Prophylaxis of Intestinal Acute Graft Versus Host Disease (aGVHD) in Participants Undergoing Allogeneic Hematopoietic Stem Cell (Allo-HSCT) Transplantation

Completed Phase 3 Results posted Last updated 6 June 2023
What this trial tests

Phase 3 trial testing Vedolizumab Placebo in Hematopoietic Stem Cells in 343 participants. Completed in 9 May 2022.

Timeline
6 February 2019
Primary endpoint
7 February 2022
9 May 2022

Quick facts

Lead sponsorMillennium Pharmaceuticals, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment343
Start date6 February 2019
Primary completion7 February 2022
Estimated completion9 May 2022
Sites139 locations across Italy, Japan, Taiwan, Poland, South Korea, Russia, Belgium, Sweden

Drugs / interventions tested

Conditions studied

Sponsor

Millennium Pharmaceuticals, Inc. — full company profile →

Who can join

12 and older, any sex, with Hematopoietic Stem Cells. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Intestinal aGvHD-Free Survival After Allo-HSCT by +180 Days Primary · From the date of first dose of study drug to first documented intestinal aGvHD or death, whichever occurs first up to +180 days

Intestinal aGvHD Free Survival is the time from the date of first study drug administration (Day-1) to intestinal aGvHD event/death, where an event is defined as death due to any cause or Stage 1-4 intestinal involvement per Acute Graft versus-Host Disease Clinical Stage criteria. Data was censored for participants who have not had the intestinal aGvHD event or died or have had the event after pre-specified timing, e.g., last contact or Day +180 after allo HSCT whichever occurs first.

GroupValue95% CI
PlaceboNA14 – 182
Vedolizumab 300 mgNA2 – 182
Intestinal aGvHD-Free and Relapse-Free Survival Secondary · From the date of first dose of study drug to first documented intestinal aGvHD, death or relapse, whichever occurs first up to Day +180

Intestinal aGvHD and Relapse Free Survival is the time from the date of first study drug administration (Day-1) to intestinal aGvHD event/death/relapse, where an event is defined as death or Stage 1-4 intestinal involvement per Acute Graft versus-Host Disease Clinical Stage criteria, or relapse. It will be censored for participants who have not had the event or have had the event after pre-specified timing, e.g., last contact or Day +180 after allo-HSCT whichever occurs first.

GroupValue95% CI
PlaceboNA14 – 182
Vedolizumab 300 mgNA2 – 182
Grade C-D aGvHD-Free Survival Secondary · From the date of first dose of study drug to first documented Grade C-D aGvHD or death, whichever occurs first up to Day +180

Grade C-D aGvHD Free Survival is the time from the date of first study drug administration (Day-1) to GvHD event/death, where an event is defined as Grade C-D aGvHD any organ involvement per International Bone Marrow Transplant Registry Database (IBMTR) Severity Index for aGvHD or death. It will be censored for participants who have not had the event or have had the event after pre-specified timing, eg, last contact or Day +180 after allo-HSCT whichever occurs first.

GroupValue95% CI
PlaceboNA12 – 182
Vedolizumab 300 mgNA12 – 182
Nonrelapse Mortality (NRM) Secondary · From the date of first dose of study drug to first documented death without relapse, up to Day +180

Non-relapse mortality is the time from the date of first study drug administration (Day-1) to death without occurrence of a relapse. Data was censored for participants who have not had the event or have had the event after pre-specified timing, e.g., last contact or Day +180 after allo HSCT whichever occurs first.

GroupValue95% CI
PlaceboNA14 – 182
Vedolizumab 300 mgNA19 – 182
Overall Survival (OS) Secondary · From the date of first dose of study drug to first documented death up to Day +180

Overall Survival by Days +180 is the time from the date of first study drug administration (Day-1) to death from any cause.

GroupValue95% CI
PlaceboNA14 – 182
Vedolizumab 300 mgNA19 – 182
Grade B-D aGvHD-Free Survival Secondary · From the date of first dose of study drug to first documented grade B-D aGvHD or death, whichever occurs first up to Day +180

Grade B-D aGvHD Free Survival is the time from the date of first study drug administration (Day-1) to aGvHD event or death, where an event is defined as death or grade B-D any organ involvement per IBMTR Severity Index for aGvHD.

GroupValue95% CI
PlaceboNA12 – 182
Vedolizumab 300 mgNA12 – 182

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug up to end of study (up to 39 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 114/165 (69%)
Deaths: 34/169
Vedolizumab 300 mg
Serious: 120/169 (71%)
Deaths: 26/174

Serious adverse events (209 terms)

ReactionSystemPlaceboVedolizumab 300 mg
Acute graft versus host disease in intestineImmune system disorders
PyrexiaGeneral disorders
SepsisInfections and infestations
Alanine aminotransferase increasedInvestigations
Acute myeloid leukaemia recurrentNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
Acute kidney injuryRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
Cytomegalovirus infection reactivationInfections and infestations
PancytopeniaBlood and lymphatic system disorders
StomatitisGastrointestinal disorders
Multiple organ dysfunction syndromeGeneral disorders
Acute graft versus host diseaseImmune system disorders
Acute graft versus host disease in liverImmune system disorders
BacteraemiaInfections and infestations
Myelodysplastic syndromeNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Respiratory failureRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
Hepatic function abnormalHepatobiliary disorders
Acute graft versus host disease in skinImmune system disorders
Septic shockInfections and infestations
Engraft failureInjury, poisoning and procedural complications
Cystitis haemorrhagicRenal and urinary disorders
Other adverse events (89 terms — click to expand)

ReactionSystemPlaceboVedolizumab 300 mg
DiarrhoeaGastrointestinal disorders
StomatitisGastrointestinal disorders
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
Acute Graft Versus Host Disease in SkinImmune system disorders
Febrile NeutropeniaBlood and lymphatic system disorders
HypomagnesaemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
VomitingGastrointestinal disorders
HypertensionVascular disorders
HypokalaemiaMetabolism and nutrition disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
Platelet Count DecreasedInvestigations
Decreased AppetiteMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Cytomegalovirus Infection ReactivationInfections and infestations
Alanine Aminotransferase IncreasedInvestigations
Back PainMusculoskeletal and connective tissue disorders
Abdominal PainGastrointestinal disorders
InsomniaPsychiatric disorders
Oedema PeripheralGeneral disorders
Blood Creatinine IncreasedInvestigations
Dry EyeEye disorders
PruritusSkin and subcutaneous tissue disorders
Aspartate Aminotransferase IncreasedInvestigations
Dry MouthGastrointestinal disorders
Blood Bilirubin IncreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Dry SkinSkin and subcutaneous tissue disorders
DizzinessNervous system disorders
DysgeusiaNervous system disorders
ErythemaSkin and subcutaneous tissue disorders
HyperglycaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Acute graft versus host disease in intestine, Pyrexia, Sepsis, Alanine aminotransferase increased, Acute myeloid leukaemia recurrent, Febrile neutropenia, Pneumonia, Acute kidney injury.

Data from ClinicalTrials.gov NCT03657160 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy of vedolizumab when added to background aGvHD prophylaxis regimen compared to placebo and background aGvHD prophylaxis regimen on intestinal aGvHD-free survival by Day +180 in participants who receive allo-HSCT as treatment for a hematologic malignancy or myeloproliferative disorder.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cell therapies in the clinic.
    Wang LL, Janes ME, Kumbhojkar N, Kapate N, et al · · 2021 · cited 99× · PMID 34027097 · DOI 10.1002/btm2.10214
  2. Treatment and unmet needs in steroid-refractory acute graft-versus-host disease.
    Malard F, Huang XJ, Sim JPY. · · 2020 · cited 98× · PMID 32242050 · DOI 10.1038/s41375-020-0804-2
  3. GVHD Prophylaxis 2020.
    Gooptu M, Antin JH. · · 2021 · cited 66× · PMID 33897681 · DOI 10.3389/fimmu.2021.605726
  4. Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial.
    Chen YB, Mohty M, Zeiser R, Teshima T, et al · · 2024 · cited 32× · PMID 38844797 · DOI 10.1038/s41591-024-03016-4
  5. Vedolizumab for prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
    Chen YB, Shah NN, Renteria AS, Cutler C, et al · · 2019 · cited 30× · PMID 31821456 · DOI 10.1182/bloodadvances.2019000893
  6. New therapeutic targets and biomarkers for acute graft-versus-host disease (GVHD).
    Choe H, Ferrara JLM. · · 2021 · cited 25× · PMID 34669521 · DOI 10.1080/14728222.2021.1992383
  7. Translational and clinical advances in acute graft-versus-host disease.
    Gooptu M, Koreth J. · · 2020 · cited 25× · PMID 33054103 · DOI 10.3324/haematol.2019.240309
  8. Challenges and opportunities targeting mechanisms of epithelial injury and recovery in acute intestinal graft-versus-host disease.
    Jansen SA, Nieuwenhuis EES, Hanash AM, Lindemans CA. · · 2022 · cited 24× · PMID 35654837 · DOI 10.1038/s41385-022-00527-6

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