Clinical Trials List
Protocol NumberVedolizumab-3035
NCT Number(ClinicalTrials.gov Identfier)NCT03657160
2018-11-01 - 2021-04-23
Phase III
Terminated7
ICD-10Z94.84
Stem cells transplant status
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vedolizumab in the Prophylaxis of Intestinal Acute Graft Versus-Host Disease in Subjects Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
Takeda Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Su-Peng Yeh Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
- Chi-Ching Chen Division of Hematology & Oncology
- Chen-Yuan Lin Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 邱倫瑋 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- YU-HSUAN SHIH Division of Hematology & Oncology
- Tsung -Chih Chen Division of Hematology & Oncology
- HSIN-CHEN LIN Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chieh-Lung Cheng Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- 田豐銘 Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Tung-Liang Lin Division of Hematology & Oncology
- Ming-Chung Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Jeng-Shiun Du Division of Hematology & Oncology
- Yi-Chang Liu Division of Hematology & Oncology
- 唐世豪 無
- Hui-Ching Wang 無
- Shih-Feng Cho 無
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Adult Ulcerative Colitis (UC); Adult Crohn′s Disease (CD); acute graft-versus-host disease (aGvHD)
Objectives
Primary Objective:
● To evaluate the efficacy and safety of vedolizumab in combination with background aGvHD prophylaxis regimen compared to placebo and background aGvHD prophylaxis regimen on intestinal aGvHD-free survival by Day +180 in subjects who receive allo-HSCT as treatment for a hematologic malignancy or myeloproliferative disorder.
Test Drug
Entyvio (Vedolizumab IV or MLN0002 IV) 300 mg/vial (60 mg/mL)
Active Ingredient
Vedolizumab
Dosage Form
Powder for Solution for Infusion
Dosage
60
Endpoints
Primary Endpoint
The primary endpoint is intestinal aGvHD-free survival by Day +180 after allo-HSCT. Intestinal
aGvHD is defined as Stage 1-4 intestinal involvement per Acute Graft-versus-Host Disease
Clinical Stage criteria .
Secondary Endpoints
The secondary endpoints are:
Intestinal aGvHD-free and relapse-free (of the underlying malignancy) survival by Day +180.
Stage 2-4 aGvHD-free (any organ involvement) survival by Day +180.
NRM by Day +180.
OS by Day +180.
Grade B-D aGvHD-free (any organ involvement) survival by Day +180.
The primary endpoint is intestinal aGvHD-free survival by Day +180 after allo-HSCT. Intestinal
aGvHD is defined as Stage 1-4 intestinal involvement per Acute Graft-versus-Host Disease
Clinical Stage criteria .
Secondary Endpoints
The secondary endpoints are:
Intestinal aGvHD-free and relapse-free (of the underlying malignancy) survival by Day +180.
Stage 2-4 aGvHD-free (any organ involvement) survival by Day +180.
NRM by Day +180.
OS by Day +180.
Grade B-D aGvHD-free (any organ involvement) survival by Day +180.
Inclution Criteria
Inclusion Criteria
Each subject must meet all the following inclusion criteria to be enrolled in the study:
1. The subject or, when applicable, the subject’s legally acceptable representative voluntarily
signs and dates a written, informed consent form (ICF) and any required privacy authorization
before performance of any study-related procedures not part of standard medical care, with the
understanding that consent may be withdrawn by the subject at any time without prejudice to
future medical care.
2. Male or female subjects 18 years of age.
3. Subjects must undergo 8 of 8 or 7 of 8 HLA-matched (antigen at HLA-A, -B, and -C, and
allelic at HLA-DRB1) unrelated hematopoietic stem cell transplantation (HSCT) from either
peripheral blood or bone marrow stem cells for a hematologic malignancy or
myeloproliferative disorder.
4. Subjects for whom a myeloablative conditioning or RIC is planned.
5. Allo-HSCT eligible (meeting institutional criteria)-subjects planned medical care should
include aGvHD prophylaxis with a combination of CNI (CYS or TAC) and MTX or CNI and
MMF. With the exception of ATG (ATG-F or thymoglobulin), all other therapies, approved or
investigational, for GvHD prophylaxis are excluded.
6. Status of the primary disease as follows:
a) Subjects with acute leukemia or chronic myelogenous leukemia: no circulating blasts and
<5% blasts in the bone marrow and minimal residual disease-negative, as per institutional
practice.
b) Subjects with myelodysplasia: no circulating blasts and 10% blasts in the bone marrow.
c) Subjects with chronic lymphocytic leukemia or small lymphocytic lymphoma with
chemosensitive disease at the time of transplantation (partial or complete response to last
salvage therapy).
d) Subjects with other nonHodgkin or Hodgkin lymphoma with a response to last salvage
therapy or chemo-sensitive disease per institutional standards at the time of
transplantation.
e) For subjects with myelofibrosis and other myeloproliferative disorders: <5% blasts in the
blood and bone marrow.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 2 (Appendix E).
8. Sufficient cognitive ability to reliably complete the PML checklist at baseline.
9. Female subjects who are:
Postmenopausal for at least 1 year before signing of the informed consent, OR
Surgically sterile, OR
If they are of childbearing potential, agree to practice 1 highly effective method of
contraception and 1 additional effective (barrier) method at the same time, from the time of
signing the informed consent through 18 weeks after the last dose of study drug, OR
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle
of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation
methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable
methods of contraception. Female and male condoms should not be used together.)
Male subjects, even if surgically sterilized (ie, status postvasectomy), who:
Agree to practice effective barrier contraception during the entire study treatment period
and through 18 weeks after the last dose of study drug, OR
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle
of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation
methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable
methods of contraception. Female and male condoms should not be used together.)
10. Suitable venous access for the study-required blood sampling, including PK sampling.
Each subject must meet all the following inclusion criteria to be enrolled in the study:
1. The subject or, when applicable, the subject’s legally acceptable representative voluntarily
signs and dates a written, informed consent form (ICF) and any required privacy authorization
before performance of any study-related procedures not part of standard medical care, with the
understanding that consent may be withdrawn by the subject at any time without prejudice to
future medical care.
2. Male or female subjects 18 years of age.
3. Subjects must undergo 8 of 8 or 7 of 8 HLA-matched (antigen at HLA-A, -B, and -C, and
allelic at HLA-DRB1) unrelated hematopoietic stem cell transplantation (HSCT) from either
peripheral blood or bone marrow stem cells for a hematologic malignancy or
myeloproliferative disorder.
4. Subjects for whom a myeloablative conditioning or RIC is planned.
5. Allo-HSCT eligible (meeting institutional criteria)-subjects planned medical care should
include aGvHD prophylaxis with a combination of CNI (CYS or TAC) and MTX or CNI and
MMF. With the exception of ATG (ATG-F or thymoglobulin), all other therapies, approved or
investigational, for GvHD prophylaxis are excluded.
6. Status of the primary disease as follows:
a) Subjects with acute leukemia or chronic myelogenous leukemia: no circulating blasts and
<5% blasts in the bone marrow and minimal residual disease-negative, as per institutional
practice.
b) Subjects with myelodysplasia: no circulating blasts and 10% blasts in the bone marrow.
c) Subjects with chronic lymphocytic leukemia or small lymphocytic lymphoma with
chemosensitive disease at the time of transplantation (partial or complete response to last
salvage therapy).
d) Subjects with other nonHodgkin or Hodgkin lymphoma with a response to last salvage
therapy or chemo-sensitive disease per institutional standards at the time of
transplantation.
e) For subjects with myelofibrosis and other myeloproliferative disorders: <5% blasts in the
blood and bone marrow.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 2 (Appendix E).
8. Sufficient cognitive ability to reliably complete the PML checklist at baseline.
9. Female subjects who are:
Postmenopausal for at least 1 year before signing of the informed consent, OR
Surgically sterile, OR
If they are of childbearing potential, agree to practice 1 highly effective method of
contraception and 1 additional effective (barrier) method at the same time, from the time of
signing the informed consent through 18 weeks after the last dose of study drug, OR
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle
of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation
methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable
methods of contraception. Female and male condoms should not be used together.)
Male subjects, even if surgically sterilized (ie, status postvasectomy), who:
Agree to practice effective barrier contraception during the entire study treatment period
and through 18 weeks after the last dose of study drug, OR
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle
of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation
methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable
methods of contraception. Female and male condoms should not be used together.)
10. Suitable venous access for the study-required blood sampling, including PK sampling.
Exclusion Criteria
Exclusion Criteria
Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.
1. Prior allo- or autologous HSCT.
2. Planned umbilical cord blood transplant or planned to receive posttransplant
cyclophosphamide, in vivo or ex vivo T cell-depleted hematopoietic stem cells (HSCs) with
the exception of ATG (ATG-F or thymoglobulin).
3. Planned allo-HSCT for nonmalignant hematological disorders (eg, aplastic anemia, sickle cell
anemia, thalassemias, Fanconi anemia or immunodeficiency).
4. Known active cerebral/meningeal disease (including central nervous system involvement of
the primary disease), or signs or symptoms of PML, any history of PML, or a positive PML
subjective checklist before the administration of study drug on Day -1.
5. Evidence of encephalopathy at screening.
6. History of any major neurological disorder, including stroke, multiple sclerosis, brain tumor,
or neurodegenerative disease.
7. Prior or current therapy with 4 and/or 7 integrin inhibitors (including, but not limited to
natalizumab, etrolizumab, AMG-181), MAdCAM-1-antibodies, anti-CD11a mAb (eg,
efalizumab) or rituximab within 60 days or 5 half-lives, whichever is longer from
randomization.
8. Prior known exposure of the transplant recipient to vedolizumab.
9. Any serious medical or psychiatric condition that could, in the investigator or medical
monitor’s opinion, potentially interfere with the completion of treatment according to this
protocol.
10. Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI, genitourinary,
coagulation, immunological, endocrine/metabolic, neurologic or other medical disorder not
related to the subject’s primary disease that, in the opinion of the investigator, would confound
the study results or compromise subject safety.
11. Clinically active systemic infection during screening.
12. Clinically active cytomegalovirus (CMV) colitis during screening.
13. Clinically active Clostridium difficile infection or other intestinal pathogen during screening.
14. Active or latent tuberculosis (TB), regardless of treatment history, as evidence by any of the
following: history of TB, OR positive QuantiFERON test or 2 successive indeterminate
QuantiFERON tests, OR a tuberculin skin test reaction 10 mm (5 mm in subjects receiving
the equivalent of >15 mg/day prednisone).
15. Chronic hepatitis B (hepatitis B surface antigen positive, or positive for both hepatitis B
surface antibody and hepatitis B core antibody but negative for hepatitis B surface antigen) or
hepatitis C infection (evident by viral replication by polymerase chain reaction).
16. History of human immunodeficiency virus (HIV) positive test.
17. Treatment with anti-T cells antibody such as alemtuzumab (anti-CD52), excluding ATG
(ATG-F or thymoglobulin), within 4 months before the first dose of study drug on Day -1.
18. Treatment with any live vaccinations within 30 days before randomization.
19. If female, the subject is pregnant, lactating or breastfeeding, or intending to become pregnant
before, during, or within 18 weeks after participating in this study, or intending to donate ova
during such time period.
20. If male, the subject intends to donate sperm during the course of this study or for 18 weeks
thereafter.
21. Diagnosed or treated for another malignancy within 2 years before the first dose of study drug
or previously diagnosed with another malignancy and have any evidence of residual disease.
Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if
they have undergone complete resection.
Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.
1. Prior allo- or autologous HSCT.
2. Planned umbilical cord blood transplant or planned to receive posttransplant
cyclophosphamide, in vivo or ex vivo T cell-depleted hematopoietic stem cells (HSCs) with
the exception of ATG (ATG-F or thymoglobulin).
3. Planned allo-HSCT for nonmalignant hematological disorders (eg, aplastic anemia, sickle cell
anemia, thalassemias, Fanconi anemia or immunodeficiency).
4. Known active cerebral/meningeal disease (including central nervous system involvement of
the primary disease), or signs or symptoms of PML, any history of PML, or a positive PML
subjective checklist before the administration of study drug on Day -1.
5. Evidence of encephalopathy at screening.
6. History of any major neurological disorder, including stroke, multiple sclerosis, brain tumor,
or neurodegenerative disease.
7. Prior or current therapy with 4 and/or 7 integrin inhibitors (including, but not limited to
natalizumab, etrolizumab, AMG-181), MAdCAM-1-antibodies, anti-CD11a mAb (eg,
efalizumab) or rituximab within 60 days or 5 half-lives, whichever is longer from
randomization.
8. Prior known exposure of the transplant recipient to vedolizumab.
9. Any serious medical or psychiatric condition that could, in the investigator or medical
monitor’s opinion, potentially interfere with the completion of treatment according to this
protocol.
10. Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI, genitourinary,
coagulation, immunological, endocrine/metabolic, neurologic or other medical disorder not
related to the subject’s primary disease that, in the opinion of the investigator, would confound
the study results or compromise subject safety.
11. Clinically active systemic infection during screening.
12. Clinically active cytomegalovirus (CMV) colitis during screening.
13. Clinically active Clostridium difficile infection or other intestinal pathogen during screening.
14. Active or latent tuberculosis (TB), regardless of treatment history, as evidence by any of the
following: history of TB, OR positive QuantiFERON test or 2 successive indeterminate
QuantiFERON tests, OR a tuberculin skin test reaction 10 mm (5 mm in subjects receiving
the equivalent of >15 mg/day prednisone).
15. Chronic hepatitis B (hepatitis B surface antigen positive, or positive for both hepatitis B
surface antibody and hepatitis B core antibody but negative for hepatitis B surface antigen) or
hepatitis C infection (evident by viral replication by polymerase chain reaction).
16. History of human immunodeficiency virus (HIV) positive test.
17. Treatment with anti-T cells antibody such as alemtuzumab (anti-CD52), excluding ATG
(ATG-F or thymoglobulin), within 4 months before the first dose of study drug on Day -1.
18. Treatment with any live vaccinations within 30 days before randomization.
19. If female, the subject is pregnant, lactating or breastfeeding, or intending to become pregnant
before, during, or within 18 weeks after participating in this study, or intending to donate ova
during such time period.
20. If male, the subject intends to donate sperm during the course of this study or for 18 weeks
thereafter.
21. Diagnosed or treated for another malignancy within 2 years before the first dose of study drug
or previously diagnosed with another malignancy and have any evidence of residual disease.
Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if
they have undergone complete resection.
The Estimated Number of Participants
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Taiwan
30 participants
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Global
558 participants
