Trial record 6 of 45 for:    vedolizumab

Dose Finding Study of Vedolizumab for Graft-Versus-Host Disease (GvHD) in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Takeda
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT02728895
First received: March 31, 2016
Last updated: August 2, 2016
Last verified: August 2016
  Purpose
The purpose of this study is to assess the initial tolerability, safety and recommended phase 2 dose of vedolizumab intravenous (IV) administered for Graft-Versus-Host Disease (GvHD) prophylaxis along with standard GvHD prophylaxis therapy (in participants undergoing allogeneic hematopoietic stem cell transplantation [allo-HSCT]).

Condition Intervention Phase
Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Vedolizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Number of Participants With Dose-Limiting Toxicities (DLT) [ Time Frame: Baseline up to Day 28 ] [ Designated as safety issue: Yes ]
    Toxicity will be evaluated according to the NCI CTCAE. DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be related to therapy with study medications. Recommended phase 2 dose is defined as a dose level at which less than 2 of 6 participants experience a dose-limiting toxicity and PK demonstrates target saturation.

  • Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 24 Weeks ] [ Designated as safety issue: Yes ]
  • Percentage of Participants Reporting One or More TEAEs and SAEs [ Time Frame: Baseline up to 24 Weeks ] [ Designated as safety issue: Yes ]
  • Trough Serum Concentrations (Ctrough) of Vedolizumab [ Time Frame: Baseline up to Day 100 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean Time to Neutrophil Engraftment [ Time Frame: Baseline up to 3 days ] [ Designated as safety issue: No ]
    Neutrophil engraftment (recovery of ANC) defined by an ANC >500/mm^3 for 3 consecutive days or >2000/mm^3 for 1 day.

  • Percentage of Participants With Overall Grade 2 to 4 Acute Graft-Versus-Host Disease (GvHD) [ Time Frame: Baseline up to 100 days ] [ Designated as safety issue: Yes ]
    As per modified Glucksberg and Blood and Marrow Transplant Clinical Trials Network (BMT CTN)-modified criteria for International Bone Marrow Transplant Registry Database (IBMTR), this is a graded scale from 1 to 4, with 1 being the least severe.

  • Percentage of Participants With Maximum Severity of Acute GvHD [ Time Frame: Baseline up to 1 year ] [ Designated as safety issue: Yes ]
    As per modified Glucksberg and Blood and Marrow Transplant Clinical Trials Network (BMT CTN)-modified criteria for International Bone Marrow Transplant Registry Database (IBMTR), this is a graded scale from 1 to 4, with 1 being the least severe.

  • Trough Serum Concentrations (Ctrough) of Vedolizumab Before Dosing [ Time Frame: Day 13 and Day 42 ] [ Designated as safety issue: No ]
    Ctrough is the mean serum concentration of vedolizumab observed from the concentration-time curve.


Estimated Enrollment: 36
Study Start Date: June 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: Vedolizumab 75 mg
Vedolizumab 75 mg, injection, intravenously once on Days -1, 13 and 42.
Drug: Vedolizumab
Vedolizumab Injection
Experimental: Cohort 2: Vedolizumab 300 mg
Vedolizumab 300 mg, injection, intravenously once on Days -1, 13 and 42.
Drug: Vedolizumab
Vedolizumab Injection
Experimental: Cohort 3: Vedolizumab Dose 1
Vedolizumab first decided dose as determined from Cohort 1 or 2, injection, intravenously once on Days -1, 13 and 42.
Drug: Vedolizumab
Vedolizumab Injection

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 UC and 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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Is undergoing matched or single-antigen mismatched unrelated-donor myeloablative transplant for the treatment of ALL or AML; Is less than or equal to (<=) 60 years of age For the cohort after Recommended phase 2 dose (RP2D)
  2. 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

Exclusion Criteria:

  1. 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.
  2. Has active cerebral/meningeal disease, active cytomegalovirus (CMV) colitis, or signs and symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML.
  3. Is undergoing transplant for the treatment of nonmalignant hematological disorders (for example: aplastic anemia, sickle cell anemia, thalassemias, Fanconi anemia).
  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: NCT02728895

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

Locations
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States
United States, New York
Not yet recruiting
Lake Success, New York, United States
United States, Ohio
Recruiting
Columbus, Ohio, United States
United States, Wisconsin
Not yet recruiting
Milwaukee, Wisconsin, United States
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02728895     History of Changes
Other Study ID Numbers: Vedolizumab-1015  U1111-1184-1822 
Study First Received: March 31, 2016
Last Updated: August 2, 2016
Health Authority: United States: Food and Drug Administration

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 August 25, 2016