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Allogeneic Hematopoietic Stem Cell TransplantationPhase 2NCT02993783

A Dose-Finding Study of Vedolizumab for Treatment of Steroid-Refractory Acute Intestinal Graft-Versus-Host Disease (GvHD) in Participants Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

A Phase 2 study testing Vedolizumab in people with Allogeneic Hematopoietic Stem Cell Transplantation, run by Millennium Pharmaceuticals, Inc. at 15 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to assess the initial activity, tolerability, safety and to identify a recommended dose and regimen of vedolizumab intravenous (IV) administered for treatment of steroid-refractory acute intestinal GvHD in participants who have undergone allo-HSCT. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vedolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
15 sitesin 5 countries
Study dates
28 Apr 2017to 9 May 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Recipient of 1 allogeneic hematopoietic stem cell transplantation (allo-HSCT) but not more than 1 allo-HSCT.
  • Has primary steroid-refractory graft-versus-host disease (GvHD). Steroid-refractory disease is defined as worsening or no improvement in 5 to 7 days of treatment with methylprednisolone 2 milligram per kilogram (mg/kg) or equivalent or lack of a CR after 14 days of primary treatment with methylprednisolone 2 mg/kg or equivalent. Note that participants who develop intestinal GvHD while receiving systemic therapy for other GvHD are still eligible after 5 to 7 days, even if the intestinal GvHD has not been present for the entire duration. Participants who may have received an increase in their steroid dose treatment (example, increased methylprednisolone from 1 mg/kg to 2 mg/kg) before enrollment will be eligible, provided the participant has met the definition of steroid refractory above. Participants who develop toxicity on corticosteroids or who are otherwise medically unable to be dosed to this level, will also be eligible.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
  • Evidence of myeloid engraftment defined by absolute neutrophil count greater than or equal to (>=) 0.5*109/liter (L) on 3 consecutive days.

Who cannot join

  • Presence of chronic GvHD at Screening (including acute-chronic overlap syndrome).
  • Relapse of underlying malignant disease after allo-HSCT.
  • Hyperacute GvHD defined as onset of GvHD within the first 15 days following hematopoietic stem cell infusion.
  • Received systemic agents other than corticosteroids for treatment of acute GvHD. GvHD prophylaxis agents (example, calcineurin inhibitors) may be continued.
  • Life expectancy of <3 weeks.

Trial locations and contacts

15 sites in 5 countries.

15 sites in 5 countries

United States6 sites
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • OSU - James Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Baylor University Medical Center

    Dallas, Texas, 75204

  • Mount Sinai - PRIME

    Lake Success, New York, 11041

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

Belgium3 sites
  • ZNA Stuivenberg

    Antwerp, 2060

  • AZ Sint-Jan Brugge

    Bruges, 8000

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

France3 sites
  • Hopital Claude Huriez - CHU Lille

    Lille, Nord, 59037

  • CHU Nantes - Hotel Dieu

    Nantes, Loire Atlantique, 44093

  • Hopital Saint-Antoine

    Paris, Paris, 75571

Other trials in France

Sweden2 sites
  • Skanes Universitetssjukhus, Lund

    Lund, 22185

  • Akademiska Sjukhuset

    Uppsala, 75185

Other trials in Sweden

Norway1 site
  • Oslo Universitetssykehus - Rikshospitalet

    Oslo, 3072

Other trials in Norway

About this study

Official title: An Open-Label, Dose-Finding Study of Vedolizumab IV for Treatment of Steroid-Refractory Acute Intestinal Graft-Versus-Host Disease (GvHD) in Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

The purpose of this study is to assess the initial activity, tolerability, safety and to identify a recommended dose and regimen of vedolizumab intravenous (IV) administered for treatment of steroid-refractory acute intestinal GvHD in participants who have undergone allo-HSCT.

Read the detailed description

The drug being tested in this study is called vedolizumab. This study will look at the tolerability and effectiveness of vedolizumab IV in participants with acute intestinal GvHD who have received no systemic therapy for the treatment of acute GvHD (prophylaxis acceptable) other than corticosteroids.

The study enrolled 17 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

  • Vedolizumab 300 mg
  • Vedolizumab 600 mg

All participants will be infused intravenously at the same time each day throughout the study. Vedolizumab IV will be administered on Days 1, 15, 43, 71, and 99. After approximately 10 participants are enrolled at each dose level and have data available from the Day 28 evaluation, safety, tolerability, efficacy, and pharmacokinetic (PK), results will be assessed for each dose level, and the appropriate dose for subsequent participants in the study will be determined.

This multi-center trial will be conducted in multiple countries. The overall time to participate in this study is 32 weeks. Participants will make multiple visits to the clinic after last dose of study drug for a follow-up assessment.

Being tested
Vedolizumab
Keywords
Drug Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VedolizumabDrug

    Also called Entyvio, MLN0002

    Vedolizumab IV infusion

Study groups in NCT02993783
Study groupRoleWhat they receive
Vedolizumab 300 mgExperimentalVedolizumab 300 mg, intravenous (IV) infusion, once on Days 1, 15, 43, 71 and 99.
Receives: Drug: Vedolizumab
Vedolizumab 600 mgExperimentalVedolizumab 600 mg, IV infusion, once on Days 1, 15, 43, 71 and 99.
Receives: Drug: Vedolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Overall Response (Partial Response [PR]+Very Good Partial Response [VGPR]+Complete Response [CR]) at Day 28

    CR is defined as the resolution of all signs and symptoms of acute graft-versus-host-disease (GvHD). VGPR is defined as resolution of the signs and symptoms of the GvHD: 1) Skin: no rash, or residual erythematous rash involving <25% of the body surface, without bullae (excluding residual faint erythema and hyperpigmentation). 2) Liver: total serum bilirubin concentration <2 mg/dL or <25% of baseline at enrollment. 3) Gut: a) participant tolerates food or enteral feeding; b) predominantly formed stools; c) no overt gastrointestinal bleeding or abdominal cramping; d) no more than occasional nausea or vomiting. PR is defined as improvement of 1 GvHD stage in 1 or more organs without progression in any organ.

    Measured: Day 28

  2. Number of Participants Who Experienced Serious Adverse Events (SAEs) Through Day 28

    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

    Measured: From first dose up to Day 28

Secondary outcomes (11)
  1. Percentage of Participants Who Died in the Absence of Primary Malignancy Relapse After Allo-HSCT at Month 6

    Measured: Month 6

  2. Percentage of Participants With Acute GvHD Complete Response (CR) at Day 28

    CR is defined as the resolution of all signs and symptoms of acute GvHD.

    Measured: Day 28

  3. Percentage of Participants With Intestinal Overall Response at Day 28

    Symptoms of acute intestinal GvHD were measured using the BMT CTN-modified International Bone Marrow Transplant Registry Database (IBMTR) index. Intestinal overall response is either CR, VGPR or PR for intestine only. CR is defined as the resolution of all signs and symptoms of GvHD. VGPR is defined as resolution of the majority of signs and symptoms of intestinal GvHD: a) participant tolerates food or enteral feeding; b) predominantly formed stools; c) no overt gastrointestinal bleeding or abdominal cramping; d) no more than occasional nausea or vomiting. PR is defined as improvement of intestinal GvHD by at least 1 stage.

    Measured: Day 28

  4. Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Months 6 and 12

    The Kaplan-Meier estimate reports the percentage of participants surviving at Months 6 and 12.

    Measured: Months 6 and 12

  5. Percentage of Participants Alive Without GvHD or Primary Malignancy Relapse at Months 6 and 12

    Measured: Months 6 and 12

  6. Total Dose of Steroids Administered

    Total Steroids administered in mg/kg/day of methylprednisolone or equivalent

    Measured: From first dose of study drug up to Months 6 and 12

  7. Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

    Measured: From first dose of study drug to 18 weeks after last dose (Up to Week 32)

  8. Number of Participants Who Experienced Serious Adverse Events (SAEs) Through Week 32

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

    Measured: From first dose of study drug to 18 weeks after last dose (Up to Week 32)

  9. Number of Participants With Markedly Abnormal Laboratory Parameters Values

    Clinical Laboratory parameters included tests for chemistry, hematology and urinalysis. Markedly abnormal values during treatment period were categorized as:alanine aminotransferase (ALT)>3.0 U/L*upper limit of normal(ULN),albumin<25 g/L*lower limit of normal(LLN),alkaline phosphatase >3.0 U/L*ULN,aspartate aminotransferase >3.0 U/L*ULN,bilirubin >2 umol/L*ULN,blood urea nitrogen(BUN) >10.7 mmol/L,calcium <1.75 mmol/L, >2.88 mmol/L,chloride <75 mmol/L, >126 mmol/L,creatinine >177umol/L,gamma glutamyl transferase (GGT) >3 U/L*ULN,glucose <2.8 mmol/L, >19.4 mmol/L,phosphate <0.52 mmol/L, >2.10 mmol/L,potassium<3 mmol/L, >6 mmol/L,sodium <130 mmol/L, >150 mmol/L,basophils >3(10^9/L)*ULN,eosinophils >2(10^9/L)*ULN,hematocrit (%) <0.8*LLN, >1.2*ULN,hemoglobin <0.8 g/L*LLN, >1.2 g/L*ULN,leukocytes <0.5 (10^9/L)*LLN, >1.5 (10^9/L)*ULN,lymphocytes <0.5 (10^9/L)*LLN, >1.5(10^9/L)*ULN,monocytes >2 (10^9/L)*ULN,neutrophils <0.5(10^9/L)*LLN, >1.5 (10^9/L)*ULN,platelets <75(10^9/L), >600(10^9/L).

    Measured: From Baseline up to last dose of study drug (Day 99)

  10. Number of Participants With Markedly Abnormal Vital Signs

    Vital signs included heart rate, respiratory rate, systolic and diastolic blood pressure, temperature and weight. The vital sign values outside the range: systolic blood pressure (SBP) <85 mmHg and change from Baseline (BL) <=-20 mmHg, >180 mmHg and change from Baseline >=20 mmHg,diastolic blood pressure (DBP) <50 mmHg and change from Baseline <=-15 mmHg, >110 mmHg and change from Baseline >=15 mmHg, heart rate <50 beats per minute (bpm),>120 beats per minute, temperature <35.6 Degree C, >37.7 Degree C and weight change from Baseline <=-7 % and weight change from Baseline >=7 % assessed during treatment period were considered markedly abnormal.

    Measured: From Baseline up to last dose of study drug (Day 99)

  11. Ctrough: Trough Serum Concentrations of Vedolizumab

    Measured: Day 99 (pre-dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Dec 2016 (estimated)
  2. Study start28 Apr 2017
  3. Primary completion9 May 2018
  4. Study completion9 May 2018

Why it stopped: Lack of efficacy of the drug; no safety concern

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02993783
Sponsor's protocol ID
Vedolizumab-2004
Other IDs
2016-002985-30, U1111-1185-6832, 2016
Status last verified
May 2019
First submitted
8 Dec 2016
Last updated
24 May 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Publications

  • Floisand Y, Schroeder MA, Chevallier P, Selleslag D, Devine S, Renteria AS, Mohty M, Yakoub-Agha I, Chen C, Parfionovas A, Quadri S, Jansson J, Akbari M, Chen YB. A phase 2a randomized clinical trial of intravenous vedolizumab for the treatment of steroid-refractory intestinal acute graft-versus-host disease. Bone Marrow Transplant. 2021 Oct;56(10):2477-2488. doi: 10.1038/s41409-021-01356-0. Epub 2021 Jun 9.

    PubMed 34108672

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vedolizumab in people with Allogeneic Hematopoietic Stem Cell Transplantation, run by Millennium Pharmaceuticals, Inc. at 15 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Belgium, France, Sweden, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Overall Response (Partial Response [PR]+Very Good Partial Response [VGPR]+Complete Response [CR]) at Day 28 (time frame: Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02993783, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2019.

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