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Allogeneic Hematopoietic Stem Cell TransplantationPhase 1NCT02728895

Dose Finding Study of Vedolizumab for GvHD in Participants Undergoing Allogeneic HSCT

A Phase 1 study testing Vedolizumab in people with Allogeneic Hematopoietic Stem Cell Transplantation, run by Takeda at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to assess the initial tolerability, safety and recommended phase 2 dose of vedolizumab intravenous (IV) administered for GvHD prophylaxis along with standard GvHD prophylaxis therapy (in participants undergoing allogeneic hematopoietic stem cell transplantation [allo-HSCT]). Read more about this study

Who is it for?
Ages 18 to 60 years
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
24 participants
Where
5 sitesUnited States
Study dates
15 Jun 2016to 10 Jul 2018
Phase
Phase 1
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 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Is undergoing matched or single-antigen mismatched unrelated-donor myeloablative transplant for the treatment of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML); Is less than or equal to (<=) 60 years of age.
  • For the cohort after RP2D
  • Is undergoing matched or single-antigen mismatched related or unrelated-donor transplant and receiving myeloablative conditioning or RIC for the treatment of hematologic malignancies or myeloproliferative neoplasms; Is less than or equal to (<=) 75 years of age.

Who cannot join

  • Has received prior allogeneic transplants or who are planned to undergo umbilical cord blood transplant, receive ex vivo T-cell-depleted hematopoietic stem cells (HSCs), received any in vivo T-cell depleting antibodies, or non-myeloablative conditioning.
  • Has active cerebral/meningeal disease, active cytomegalovirus (CMV) colitis, or signs and symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML.
  • Is undergoing transplant for the treatment of nonmalignant hematological disorders (for example: aplastic anemia, sickle cell anemia, thalassemias, Fanconi anemia).

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 2215

  • OSU - James Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Medical College of Wisconsin, Inc.

    Milwaukee, Wisconsin, 53266

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: An Open-Label, Dose-Finding Study of Vedolizumab IV Plus Standard of Care for Graft-Versus-Host Disease (GvHD) Prophylaxis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

The purpose of this study is to assess the initial tolerability, safety and recommended phase 2 dose of vedolizumab intravenous (IV) administered for GvHD prophylaxis along with standard GvHD prophylaxis therapy (in participants undergoing allogeneic hematopoietic stem cell transplantation [allo-HSCT]).

Read the detailed description

The drug being tested in this study is called Vedolizumab. Vedolizumab (also called MLN0002) is approved for the treatment of adult participants with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) who achieved an inadequate response, had a loss of response, or were intolerant to conventional and/or biologic treatments. This study will look at the tolerability and pharmacokinetics of Vedolizumab in participants undergoing allo-HSCT when added to standard GvHD prophylaxis (tacrolimus plus short-term methotrexate) for the prevention of acute GvHD (major complication in allo-HSCT).

The study will enroll approximately 36 participants. Participants will be assigned to different dose-escalating cohorts in order to find out the recommended phase 2 dose (RP2D) of the study:

  • Cohort 1: Vedolizumab 75 mg
  • Cohort 2: Vedolizumab 300 mg
  • Cohort 3: Vedolizumab Dose 1

All participants have to receive 1 injection of Vedolizumab on Day -1 before allo-HSCT and on Days 13 and 42 after allo-HSCT. If none of the participants receiving vedolizumab at 75 mg experience dose-limiting toxicities (DLTs), dose escalation will continue to 300 mg on Day -1 before allo-HSCT and on Days +13 and +42 after allo-HSCT. If the first 3 participants at 300 mg tolerate the treatment without experiencing DLTs, then the decision on whether to increase the vedolizumab IV dose in the next cohort will be guided by the PK results.

Cohorts will be escalated in same manner until the identification of RP2D. The cohort at that dose level may be expanded to include approximately 18 additional participants undergoing myeloablative conditioning or reduced-intensity conditioning (RIC) and receiving either related or unrelated allo-HSCT for the treatment of hematologic malignancies or myeloproliferative neoplasms. This group of participants will allow the further assessment of the tolerability and clinical activity of vedolizumab.

This multi-center trial will be conducted in the United States. The overall time to participate in this study will be approximately 2 years. Following the treatment period, participants who remain in remission will be followed for development of acute and chronic GvHD and safety during clinic visits at 4, 5, 6, 9, and 12 months after allo-HSCT or until death or withdrawal of consent or termination of the study by the sponsor. Participants who complete the study will attend a 12-month follow-up visit. Patients who have been discontinued from treatment will attend an end of treatment visit 30 to 40 days after the last dose of study drug using all study procedures outlined for the 12-month follow-up visit.

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

    Vedolizumab Injection.

Study groups in NCT02728895
Study groupRoleWhat they receive
Cohort 1: Vedolizumab 75 mgExperimentalVedolizumab 75 mg, injection, intravenously once on Days -1, 13 and 42.
Receives: Drug: Vedolizumab
Cohort 2: Vedolizumab 300 mgExperimentalVedolizumab 300 mg, injection, intravenously once on Days -1, 13 and 42.
Receives: Drug: Vedolizumab
Cohort 3: Vedolizumab Dose 1ExperimentalVedolizumab first decided dose as determined from Cohort 1 or 2, injection, intravenously once on Days -1, 13 and 42.
Receives: Drug: Vedolizumab

What is being measured

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

  1. Number of Participants With Dose-Limiting Toxicities (DLTs)

    DLTs was based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and was defined as any of following events: Grade 3 or higher toxicity assessed by the investigator as related to vedolizumab treatment; Grade 4 or higher regimen-related organ toxicities; and failure to engraft by Day +28. Engraftment was defined as absolute neutrophils count (ANC) greater than (>) 500 per cubic millimeter (/mm^3) for 3 consecutive days or >2000/mm^3 for 1 day.

    Measured: Baseline up to Day 28

  2. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Measured: Up to 18 weeks after last dose of study drug

  3. Mean Serum Concentrations of Vedolizumab That Helped the Likelihood of Alpha4Beta7 Target Saturation on Day 100 Following Allo-HSCT

    Measured: Day 100

Secondary outcomes (5)
  1. Time to Neutrophil Engraftment

    Time to neutrophil engraftment (recovery of ANC) was defined by an ANC >500/mm^3 for 3 consecutive days or >2000/mm^3 for 1 day. Time to neutrophil engraftment was calculated using Kaplan-Meier estimate and presented with 2-sided 95% confidence interval.

    Measured: Baseline up to Day 100

  2. Percentage of Participants With Overall Grade 2 to 4 Acute Graft-Versus-Host Disease (GvHD)

    GvHD grading scale was based on the modified Glucksberg criteria. The grades are defined as: Grade 1 (skin stage 1 or 2 only); Grade 2 (skin stage 3 or liver stage 1 or lower or gastrointestinal [GI] stage 1 or upper GI involvement); Grade 3 (skin stage 0 to 3 plus liver stage 2 to 4 or lower GI stage 2 to 3); Grade 4 (skin stage 4 or lower GI stage 4).

    Measured: Baseline up to Day 100

  3. Percentage of Participants With Maximum Severity of Acute GvHD Based on Modified Glucksberg Criteria

    Maximum severity was assessed using GvHD grading scale based on the modified Glucksberg criteria. The grades are defined as: Grade 1 (skin stage 1 or 2 only); Grade 2 (skin stage 3 or liver stage 1 or lower or GI stage 1 or upper GI involvement); Grade 3 (skin stage 0 to 3 plus liver stage 2 to 4 or lower GI stage 2 to 3); Grade 4 (skin stage 4 or lower GI stage 4).

    Measured: Baseline up to Day 100

  4. Percentage of Participants With Maximum Severity of Acute GvHD Based on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Modified International Bone Marrow Transplant Registry Database (IBMTR) Index

    Maximum severity of acute GvHD was assessed by using BMT CTN modified IBMTR index. The severity index are defined as: Grade A (skin stage 1: extent of rash less than [<] 25%); Grade B (skin stage 2: extent of rash 25 to 50% or liver stage 1 to 2: total bilirubin 34 to 102 micromole per liter [mcmol/L] or intestinal tract stage 1 to 2: volume of diarrhea 550 to 1500 milliliter per day [mL/day]); Grade C (skin stage 3: extent of rash greater than (>) 50% or liver stage 3: total bilirubin 103 to 255 mcmol/L or intestinal tract stage 3: volume of diarrhea >1500 mL/day); Grade D (skin stage 4: extent of rash bullae or liver stage 4: total bilirubin >255 or intestinal tract stage 4: volume of diarrhea severe pain and ileus).

    Measured: Baseline up to Day 100

  5. Ctrough: Serum Concentration Before Dosing for Vedolizumab

    Measured: Days 13 and 42 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 posted5 Apr 2016 (estimated)
  2. Study start15 Jun 2016
  3. Primary completion10 Jul 2018
  4. Study completion10 Jul 2018

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02728895
Sponsor's protocol ID
Vedolizumab-1015
Other IDs
U1111-1184-1822
Status last verified
Jul 2019
First submitted
31 Mar 2016
Last updated
26 Aug 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

  • Chen YB, Shah NN, Renteria AS, Cutler C, Jansson J, Akbari M, Chen C, Quadri S, Parfionovas A, Devine SM. Vedolizumab for prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019 Dec 10;3(23):4136-4146. doi: 10.1182/bloodadvances.2019000893.

    PubMed 31821456

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vedolizumab in people with Allogeneic Hematopoietic Stem Cell Transplantation, run by Takeda at 5 sites in United States.

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 3 inclusion and 3 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: finished, as of the sponsor's last update on 26 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 26 Aug 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?

Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Baseline up to Day 28). The study lists 3 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 NCT02728895, 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 26 Aug 2019.

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