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Trial record 2 of 56 for:    vedolizumab

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)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2017 by Takeda
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier:
NCT02993783
First received: December 8, 2016
Last updated: February 14, 2017
Last verified: February 2017
  Purpose
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.

Condition Intervention Phase
Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Vedolizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Participants With Overall Response (Partial Response+Very Good Partial Response+Complete Response) at Day 28 [ Time Frame: Day 28 ]

    Complete Response (CR) is defined as the resolution of all signs and symptoms of acute graft-versus-host-disease (GvHD). Very good partial response (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. Partial Response (PR) is defined as improvement of 1 GvHD stage in 1 or more organs without progression in any organ.


  • Number of Participants Reporting One or More Serious Adverse Events (SAEs) Through Day 28 [ Time Frame: Up to 28 days ]
    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. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.


Secondary Outcome Measures:
  • Percentage of Participants who Died in the Absence of Primary Malignancy Relapse After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) at Month 6 [ Time Frame: Month 6 ]
  • Percentage of Participants with Complete Response at Day 28 [ Time Frame: Day 28 ]
    CR is defined as the resolution of all signs and symptoms of acute GvHD.

  • Percentage of Participants with Intestinal Overall Response at Day 28 [ Time Frame: Day 28 ]
    Complete Response (CR) is defined as the resolution of all signs and symptoms of gastrointestinal acute graft-versus-host-disease (GvHD). Very good partial response (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. Partial Response (PR) is defined as improvement of intestinal GvHD by at least 1 stage.

  • Overall Survival (OS) at Months 6 and 12 [ Time Frame: Months 6 and 12 ]
    OS is defined as the time from the date of enrollment to the date of death, due to any cause.

  • Percentage of Participants who are Alive Without GvHD or Primary Malignancy Relapse at Months 6 and 12 [ Time Frame: Months 6 and 12 ]
  • Number of Participants Who Experience Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 32 Weeks ]
    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 (e.g., 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.

  • Number of Participants Reporting One or More Serious Adverse Events (SAEs) Through Week 32 [ Time Frame: Up to 32 Weeks ]
    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. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.

  • Trough Serum Concentrations of Vedolizumab (Ctrough) Before Dosing on Day 99 [ Time Frame: Day 99 (pre-dose) ]
  • Total Dose of Steroids Administered [ Time Frame: Up to 12 months ]

Estimated Enrollment: 38
Study Start Date: February 2017
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vedolizumab 300 mg
Vedolizumab 300 mg, infusion, intravenously once on Days 1, 15, 43, 71 and 99.
Drug: Vedolizumab
Vedolizumab intravenous infusion
Other Names:
  • Entyvio
  • MLN0002
Experimental: Vedolizumab 600 mg
Vedolizumab 600 mg, infusion, intravenously once on Days 1, 15, 43, 71 and 99.
Drug: Vedolizumab
Vedolizumab intravenous infusion
Other Names:
  • Entyvio
  • MLN0002

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 will enroll approximately 38 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

  • Vedolizumab IV 300 mg
  • Vedolizumab IV 600 mg

All participants will be infused intravenously at the same time each day throughout the study.

This multi-center trial will be conducted in multiple countries. The overall time to participate in this study is 36 months. Participants will make multiple visits to the clinic after last dose of study drug for a follow-up assessment.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Recipient of 1 allogeneic hematopoietic stem cell transplantation (allo-HSCT) but not more than 1 (allo-HSCT).
  2. Has primary steroid-refractory intestinal 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 mg/kg or equivalent or lack of a complete response (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 (e.g., 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.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
  4. Evidence of myeloid engraftment defined by absolute neutrophil count ≥0.5*109/L on 3 consecutive days.

Exclusion Criteria:

  1. Presence of chronic GvHD at Screening (including acute-chronic overlap syndrome).
  2. Relapse of underlying malignant disease after allo-HSCT.
  3. Hyperacute GvHD defined as onset of GvHD within the first 15 days following hematopoietic stem cell infusion.
  4. Received systemic agents other than corticosteroids for treatment of acute GvHD. GvHD prophylaxis agents (e.g., calcineurin inhibitors) may be continued.
  5. Acute steroid-resistant GvHD beyond 28 days from primary treatment.
  6. Life expectancy of <3 weeks.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02993783

Contacts
Contact: Takeda Study Registration Call Center +1-866-835-2233 GlobalOncologyMedinfo@takeda.com

Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Director Millennium Pharmaceuticals, Inc.
  More Information

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02993783     History of Changes
Other Study ID Numbers: Vedolizumab-2004  2016-002985-30  U1111-1185-6832 
Study First Received: December 8, 2016
Last Updated: February 14, 2017

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Vedolizumab
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 24, 2017