Dose Finding Study of Vedolizumab for GvHD in Participants Undergoing Allogeneic HSCT
|ClinicalTrials.gov Identifier: NCT02728895|
Recruitment Status : Completed
First Posted : April 5, 2016
Results First Posted : August 26, 2019
Last Update Posted : August 26, 2019
|Condition or disease||Intervention/treatment||Phase|
|Allogeneic Hematopoietic Stem Cell Transplantation||Drug: Vedolizumab||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||June 15, 2016|
|Actual Primary Completion Date :||July 10, 2018|
|Actual Study Completion Date :||July 10, 2018|
Experimental: Cohort 1: Vedolizumab 75 mg
Vedolizumab 75 mg, injection, intravenously once on Days -1, 13 and 42.
Experimental: Cohort 2: Vedolizumab 300 mg
Vedolizumab 300 mg, injection, intravenously once on Days -1, 13 and 42.
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.
- Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Baseline up to Day 28 ]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.
- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 18 weeks after last dose of study drug ]
- Mean Serum Concentrations of Vedolizumab That Helped the Likelihood of Alpha4Beta7 Target Saturation on Day 100 Following Allo-HSCT [ Time Frame: Day 100 ]
- Time to Neutrophil Engraftment [ Time Frame: Baseline up to Day 100 ]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.
- Percentage of Participants With Overall Grade 2 to 4 Acute Graft-Versus-Host Disease (GvHD) [ Time Frame: Baseline up to Day 100 ]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).
- Percentage of Participants With Maximum Severity of Acute GvHD Based on Modified Glucksberg Criteria [ Time Frame: Baseline up to Day 100 ]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).
- 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 [ Time Frame: Baseline up to Day 100 ]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).
- Ctrough: Serum Concentration Before Dosing for Vedolizumab [ Time Frame: Days 13 and 42 pre-dose ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02728895
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 2215|
|United States, New York|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|United States, Ohio|
|OSU - James Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Wisconsin|
|Medical College of Wisconsin, Inc.|
|Milwaukee, Wisconsin, United States, 53266|
|Study Director:||Medical Director||Takeda|