Autologous Stem Cell Transplant for Crohn's Disease
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|ClinicalTrials.gov Identifier: NCT03219359|
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : August 25, 2020
Crohn's Disease (CD) is an inflammatory bowel disease. It can lead to significant complications and discomfort in the stomach and intestines. Crohn's disease is a debilitating, incurable disease of immune cells; it affects almost 1 million people in the United States. CD is characterized by inflammation of the stomach and intestine as well as organs outside of the intestines such as the skin, eyes, and joints. Current therapies to treat CD aim to suppress the patient's immune cells but these therapies become ineffective for the majority of patients and lead to complications including the requirement for surgical bowel resection, impaired quality of life, and lifelong disability. Hematopoietic stem cell transplantation (HCT) is a procedure used to treat a number of medical conditions including Crohn's disease. To improve success of HCT in CD doctors considered combining transplant with other drugs to improve the chances of achieving remission and also maintaining the remission. The Investigators' plan in this study is to incorporate the drug Vedolizumab after transplant to test if this drug will improve remission and make patients healthier.
Patients may qualify to take part in this research study because Crohn's disease is active, because surgery is not a treatment option and because there is evidence that the disease has failed to respond to treatments for Crohn's disease including the following:
- azathioprine, 6-mercaptopurine, methotrexate
- Anti-TNFα (infliximab, adalimumab, certolizumab, golimumab)
- Anti-integrin agents (natalizumab, Vedolizumab) If patients meet entry criteria will undergo a baseline endoscopy, colonoscopy and MR or CT enterography. If documentation of active mucosal disease patients will then be tapered off of current medications and undergo stem cell mobilization. Mobilization will involve low dose chemotherapy, growth factors and require 1-2 week hospitalization. Patients will then undergo stem cell transplant which will involve high dose chemotherapy and require a 2-4 week hospitalization. After restoration of the immune system patients will be placed on vedolizumab per standard dosing (0,2,6 then 8 every weeks) for a total of 8 doses. Patients will have monthly study visits and a repeat colonoscopy and MR/CT scan at 6 months.
|Condition or disease||Intervention/treatment||Phase|
|Crohn Disease||Procedure: Autologous stem cell transplant Drug: Cyclophosphamide Drug: Thymoglobulin Drug: Methylprednisolone Drug: Vedolizumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Maintenance in Autologous Stem Cell Transplant for Crohn's Disease (MASCT - CD)|
|Actual Study Start Date :||July 12, 2017|
|Estimated Primary Completion Date :||August 2022|
|Estimated Study Completion Date :||August 2022|
Hematopoietic Stem Cell Transplant followed by maintenance Vedolizumab
Procedure: Autologous stem cell transplant
Hematopoietic stem cell transplantation
Other Name: Bone Marrow Transplant
Days 1 and 2: Cyclophosphamide 2gm/m2/day x 2 days (total dose 4gm/m2) Day 3 until leukapheresis: G-CSF 10μg/kg/day to CD34+ >20x104/ml then leukapheresis daily to collection goal
Day -5 to -2: Cyclophosphamide 50 mg/kg/day (200 mg/kg total dose)
Day -3 to -1: 2.5 mg/kg/day (7.5 mg/kg total dose)
Other Name: ATG
Day -3 to -1: 1mg/kg prior to each ATG dose
Starting first day after discharge from transplant admission, then 2 weeks after 1st infusion, 4 weeks after 2nd infusion, followed by every 8 weeks for 52 weeks (8 doses)
- Change in Crohn's Disease Activity Index (CDAI) [ Time Frame: baseline and 1 year post transplant ]The proportion of patients in clinical remission, defined as a CDAI < 150, one year after autologous HCT from 45% to 65% as compared to baseline.
- Change in endoscopic activity indices [ Time Frame: baseline and 1 year post transplant ]The change in endoscopic activity indices (SES CD) following autologous HCT and vedolizumab maintenance as compared to baseline.The maximal score for the SES-CD is 56. Each of 5 segments of intestine (rectum, colon - descending, colon - ascending, colon - transverse, ileum) is scored from 0-3 on four parameters - ulceration, extent of ulceration, extent of disease and stenosis. A maximal score of 45 is possible for the first three parameters and 11 for stenosis as a score of 3 implies a stricture that cannot be traversed prohibiting evaluation of later segments. An SES score of 0-2 would be defined as mucosal healing as the presence of a single ulcer in one bowel segment would necessitate a minimal score of 3. A decrease of SES of 50% from baseline is felt to represent an endoscopic response.
- Change in burden of intestinal disease [ Time Frame: baseline and 1 year post transplant ]The change in overall burden of intestinal disease (Magnetic resonance enterography ((MRE)+SES-CD) following autologous HCT and vedolizumab maintenance as compared to baseline.
- Change in Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: baseline and 1 year post transplant ]The change in quality of life indices as evaluated via the IBDQ following autologous HCT and vedolizumab maintenance as compared to baseline. An increase in the IBD-Q of 16-32 points is generally considered meaningful.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03219359
|Contact: Artur Shchukinfirstname.lastname@example.org|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Alex Abrahams 212-241-8233 email@example.com|
|Principal Investigator: Amir Steinberg, MD|
|Principal Investigator: Louis Cohen, MD|
|Principal Investigator:||Amir Steinberg, MD||Icahn School of Medicine at Mount Sinai|
|Principal Investigator:||Louis Cohen, MD||Icahn School of Medicine at Mount Sinai|