Vedolizumab in Subjects Undergoing Stem Cell Transplantation
Research type
Research Study
Full title
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
IRAS ID
251531
Contact name
Amit Patel
Contact email
Sponsor organisation
Millennium Pharmaceuticals Inc.
Eudract number
2018-002141-11
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
009125, IND Number
Duration of Study in the UK
2 years, 1 months, 13 days
Research summary
Summary of Research
Allogenic stem cell transplant involves taking healthy stem cells from the blood or bone marrow of a healthy person (ideally with the same or similar tissue type) and transferring them to the patient. Haematopoeitic stem cells are cells that will produce new blood cells.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT), is an important and potentially curative therapy for many haematologic malignancies (forms of cancer in the cells of blood-forming tissues), but its use is limited by the major complication of graft-versus-host disease (GvHD). This occurs when the transplanted cells start to attack the other cells in the patients body. GvHD is a common and a major cause of allo-HSCT morbidity and mortality.
Treatment to prevent GvHD is given to all patients undergoing allo-HSCT; however, use of these agents can delay immune recovery and increase the risk of infection and relapse. Reducing the risk of developing GvHD has the potential to improve overall outcomes in allo-HSCT and possibly extend and/or save lives from this rare disease.
Inflammation and damage to the gastrointestinal (GI) tract is a major mechanism for amplification of acute GvHD and several key similarities exist with other immune-mediated diseases like inflammatory bowel disease (IBD). Vedolizumab is a monoclonal antibody which inhibits white blood cell activity in the GI tract. Studies suggest that vedolizumab may reduce the severity and intensity of intestinal GvHD.
The objective of this proposed study is to evaluate the efficacy and safety of vedolizumab when added to a background acute GvHD prophylaxis regimen for intestinal aGvHD in patients undergoing allo-HSCT.
Approximately 558 participants will be randomised in a 1:1 fashion to 2 treatment arms (vedolizumab or placebo). The study consists of a 28-day screening period, 155-day treatment period, a visit on Day +180 after allo-HSCT, and a 12-month follow-up period for safety assessments and survival.
Summary of Results
Thank you to the participants who took part in the study called “Vedolizumab in the Prophylaxis of Intestinal Acute Graft Versus Host Disease (aGvHD) in Participants Undergoing Allogenic Hematopoietic Stem Cell (Allo-HSCT) Transplantation”.
This study helped researchers learn about the efficacy of vedolizumab to prevent gastrointestinal aGvHD symptoms in participants who had a stem cell transplant.
Why was this study done?
Blood cancer is a type of cancer that occurs when uncontrolled growth of abnormal blood cells overtakes the development of normal blood cells. There are different ways to treat blood cancer. One way is a stem cell transplant from someone who donates blood or bone marrow.Stem cells are found in the peripheral blood and the bone marrow. Bone marrow is the soft, spongy center of the bone. These stem cells develop into all types of blood cells, including white blood cells, red blood cells, and platelets. The donor stem cells are transplanted into a patient to treat or cure certain types of blood cancer.
After a stem cell transplant, the patient may get graft versus host disease (GvHD). GvHD is caused by the transplanted cells attacking the patient’s cells. This happens because the transplanted stem cells do not recognize the new body. GvHD can cause severe, life-threatening symptoms.
Parts of the body affected by GvHD include the skin, liver, and gastrointestinal tract. The gastrointestinal tract includes the mouth, esophagus, stomach, intestines, colon, and anus.
Common symptoms include rash, nausea, yellowing of the skin or eyes, and abdominal cramps with diarrhea. Patients with GvHD can have other symptoms as well.GvHD can be acute or chronic based on when symptoms start. Acute GvHD (aGvHD) is when symptoms start within 100 days of a stem cell transplant.
The medication used in this study is called vedolizumab. Researchers wanted to learn more about vedolizumab in participants who had received a stem cell transplant. They wanted to know if vedolizumab, when added to standard treatment, could lower the risk of participants having gastrointestinal aGvHD symptoms or dying.
When was this study done?
This study started in February 2019 and ended in May 2022.Who took part in this study?
Who was allowed to take part in this study?
Participants could take part if they:
• Were 12 years of age or older
• Had DNA testing and a stem cell transplant for blood cancerFor more information on who could take part in this study, please refer to the websites listed on the last page of this summary.
How many people took part in this study?
There were 343 participants who took part in the study. However, results were reported for only 333 participants who received at least 1 dose of study drug and underwent stem cell transplant. There were 209 (63%) men and 124 (37%) women. Participants were between 16 and 74 years old.The study took place at 25 countries. The list of countries is shown below.
Countries where the study took place
Australia Canada Israel Portugal Spain
Argentina France Italy Republic of Korea Sweden
Austria Germany Japan Romania Switzerland
Belgium Greece Norway Russia United Kingdom
Brazil Hungary Poland Singapore United StatesWhat happened during the study?
What did researchers want to know?
Researchers wanted to know if vedolizumab could prevent gastrointestinal symptoms of aGvHD in participants who had a stem cell transplant.All participants also received standard treatment to prevent aGvHD. Standard treatment included 2 or 3 medications. They were either cyclosporin or tacrolimus, and either methotrexate or mycophenolate mofetil. Participants could also receive antithymocyte globulin if recommended by their doctor.
Researchers recorded information on any side effects participants experienced.
What treatments were studied?
Researchers studied 2 treatment groups in addition to standard treatment to prevent aGvHD after a stem cell transplant. They were:
• Vedolizumab: 300 mg, given as a slow injection into a vein • Placebo: given as a slow injection into a vein A placebo is a drug that looks like the study drug but does not contain any medication.How was the study done?
There are many types of clinical studies. This study was:
• Phase 3: In a Phase 3 study, a treatment is tested in a large number of participants.
• Randomized: Who received which dose of medicine was decided randomly by a computer program.
• Double-Blind: Researchers and patients did not know who was getting study drug and who received placebo.Before treatment, all participants were screened to be sure they were a good fit for the study. The screening included physical examination and laboratory tests. The screening period lasted up to 30 days.
After screening, participants were randomly placed in 1 of 2 treatment groups. The number of participants in each group are given in the table below.
Placebo plus standard treatment = 169 participants Vedolizumab plus standard treatment = 174 participants
Participants received 7 doses of vedolizumab or placebo plus standard treatment over 155 days, or about 5 months.
They received the first dose the day before the donor stem cell transplant.
Researchers monitored participants’ health for 12 months after the transplant or until the study ended.What were the results?
Participants received their dose of vedolizumab or placebo. Researchers recorded any gastrointestinal aGvHD symptoms after a stem cell transplant. For the first 180 days, they also recorded:
• How long it took for participants to have symptoms • If a participant died for any reasonResearchers decided if a participant was having gastrointestinal aGvHD symptoms using standard checklists used by doctors. Gastrointestinal aGvHD symptoms include diarrhea and abdominal pain.
The results included 333 participants who received at least 1 dose of study drug and underwent stem cell transplant.
Gastrointestinal aGvHD symptoms or death in participants receiving Placebo plus standard treatment (165 participants):
- Gastrointestinal aGvHD symptoms = 31 (19%)
- Death from any cause = 16 (10%)
- Total = 47 (29%)Gastrointestinal aGvHD symptoms or death in participants receiving Vedolizumab plus standard treatment (168 participants):
- Gastrointestinal aGvHD symptoms = 12 (7%)
- Death from any cause = 12 (7%)
- Total = 24 (14%)For more information on study results, please refer to the websites listed on the last page of this summary.
Were there any drug-related side effects?
Side effects are unwanted medical problems thought to be caused by a medicine or medical treatment. Not all participants had side effects. The results included 334 participants who received at least 1 dose of study drug.The table below shows how many participants in each group had drug-related side effects.
Drug-related side effects in participants receiving Placebo plus standard treatment (165 participants):
- Participants with any side effects = 41 (25%)
- Participants with serious side effects = 14 (8%)
- Participants who left the study due to side effects = 10 (6%)
- Deaths = 0Drug-related side effects in participants receiving Vedolizumab plus standard treatment (168 participants):
- Participants with any side effects = 48 (28%)
- Participants with serious side effects = 11 (7%)
- Participants who left the study due to side effects = 7 (4%)
- Deaths = 0A side effect is called ‘serious’ when it is life threatening, causes lasting problems, or needs hospital care.
Only the serious side effects that occurred in at least 2 participants were reported. In the placebo plus standard treatment there were 2 out of 165 (1%) participants who had abnormal liver function. In the vedolizumab plus standard treatment, there was no serious side effect that affected at least 2 participants.
The table below shows how many participants in each group had the most common side effects. Only side effects experienced by at least 2% of participants were included.
Most common drug-related side effects in participants receiving Placebo plus standard treatment (165 participants):
- Increased level of aspartate aminotransferase, a liver protein in the blood = 3 (2%)
- Increased level of alanine aminotransferase, a liver protein in the blood = 5 (3%)
- Abdominal pain = 3 (2%)
- Fever = 1 (1%)
- High levels of bilirubin in the blood = 0
- Abnormal liver function = 3 (2%)
- Acute GvHD in the intestines = 3 (2%)Most common drug-related side effects in participants receiving Vedolizumab plus standard treatment (169 participants):
- Increased level of aspartate aminotransferase, a liver protein in the blood = 5 (3%)
- Increased level of alanine aminotransferase, a liver protein in the blood = 4 (2%)
- Abdominal pain = 3 (2%)
- Fever = 3 (2%)
- High levels of bilirubin in the blood = 3 (2%)
- Abnormal liver function = 1 (1%)
- Acute GvHD in the intestines = 1 (1%)How has this study helped patients and researchers?
Researchers look at the results of many studies to decide which medicines work best and are safest for patients. This summary gives the results for 334 participants in a single study. Other studies may show different results.Findings from this study may be used to learn whether patients are helped by this treatment.
Are there plans for further studies?
Other clinical studies with vedolizumab are ongoing and further studies are planned.Where can I find out more about this study?
Title of this study: A Randomized, Double-Blind, Placebo-Controlled, Multi-center 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
Protocol number: Vedolizumab-3035
EU study number: 2018-002141-11
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https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BcbW9wgc64X2JjNxW-2BqMpAMnbRZlgsjMrY5YpxpscbOgA-3D-3DJBuu_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIpYql8LQaGs-2BPH8zYAAPiHdsN3n5yrlLMtvvaZeJs-2Fqa0S3aUycOAnueP9k7bwVclXzn4MKiQk-2BjTM5Ld5BP7EIkhfdlbnrZUzulPmnTaepXD3qepeTPwClgFOf-2BGMAxlJAhPfYlI1i9062cKvFL1SM7akUWjCYbH2K8fNaQX23g-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cce58ad8faa964cab085b08daf2fbcb85%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638089460513853334%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=k0FEHyI0G811TnvLcAA%2BCE4OKbNhzzJbt2HMAydnAbg%3D&reserved=0Millennium Pharmaceuticals, Inc. (a subsidiary of Takeda) is the sponsor of this study.
Takeda has its headquarters in Nihonbashi, Tokyo in Japan.
More information about this study can be found at: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agba4yu73OCS9U-2BkKS40W1kfaoh9WIaQNJSp0sxK-2BovfY3Z6Y8_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIpYql8LQaGs-2BPH8zYAAPiHac-2B3FP0gq-2FumuqeJHTv83iTcaMvN2DwiuBbt7Oozkfd3t-2FgB7XUgeDMAa3yzVqc3BrJUaHvz5gUseoqe3AqNbzxczQYlE7TpqSzKmaYcJZ-2Fpl1C9yQpjnwMDwEDXGjUwgTXs25TyzrI6WBSHJY3dEA-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cce58ad8faa964cab085b08daf2fbcb85%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638089460513853334%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=ECuSxVEC%2BXg%2FGdkKoIqdQV1aPZTi3RKEQ5MAxGG4sRI%3D&reserved=0REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
18/EM/0323
Date of REC Opinion
21 Dec 2018
REC opinion
Further Information Favourable Opinion