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Autologous Stem Cell Transplant for Crohn's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03219359
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : August 25, 2020
Sponsor:
Information provided by (Responsible Party):
Amir Steinberg, Icahn School of Medicine at Mount Sinai

Brief Summary:

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:

  • corticosteroids
  • 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: Experimental
Hematopoietic Stem Cell Transplant followed by maintenance Vedolizumab
Procedure: Autologous stem cell transplant
Hematopoietic stem cell transplantation
Other Name: Bone Marrow Transplant

Drug: Cyclophosphamide
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

Drug: Cyclophosphamide
Day -5 to -2: Cyclophosphamide 50 mg/kg/day (200 mg/kg total dose)

Drug: Thymoglobulin
Day -3 to -1: 2.5 mg/kg/day (7.5 mg/kg total dose)
Other Name: ATG

Drug: Methylprednisolone
Day -3 to -1: 1mg/kg prior to each ATG dose

Drug: Vedolizumab
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)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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.

  2. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Crohn's disease by standard criteria
  • Active disease based on clinical symptoms, defined as CDAI >250. In patients with an ostomy, the number of liquid stools score in the CDAI will be replaced by the number of times that the ostomy bag is emptied daily.
  • Active disease based on endoscopic evaluation, defined as SES-CD score > 3 in at least one bowel segment
  • Failure to respond to (or intolerant/adverse reaction to or declines) a member of each of the class of drugs listed below:

    1. corticosteroids
    2. azathioprine,
    3. 6-mercaptopurine, methotrexate
    4. Anti-TNFα (infliximab, adalimumab, certolizumab, golimumab)
    5. Anti-integrin agents (natalizumab, vedolizumab)
    6. Ustekinumab
  • Failure to respond refers to ongoing objective inflammation with symptoms and, as is traditional, is defined by the gastroenterologist evaluating the patient.
  • No surgical therapeutic option secondary to risk of short bowel syndrome or patient refusal

Exclusion Criteria:

  • History of significant toxicity to any medications used in trial (cyclophosphamide, thymoglobulin, vedolizumab)
  • Pregnant or breastfeeding
  • Age <18
  • Karnofsky Performance Score <60
  • Patients who have an uncontrolled infection (presumed or documented) despite appropriate therapy for at least one month
  • Patients with symptomatic coronary artery disease or uncontrolled congestive heart failure.
  • HIV infected
  • Ejection fraction <30% or requiring supplemental continuous oxygen.
  • DLCO <35% or requiring supplementary oxygen.
  • Patients for whom an insufficient number of stem cells (<2 X 10^6/kg) have been collected.

Information from the National Library of Medicine

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


Contacts
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Contact: Artur Shchukin 212-241-0497 artur.shchukin@mssm.edu

Locations
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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    alex.abrahams@mssm.edu   
Principal Investigator: Amir Steinberg, MD         
Principal Investigator: Louis Cohen, MD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Investigators
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Principal Investigator: Amir Steinberg, MD Icahn School of Medicine at Mount Sinai
Principal Investigator: Louis Cohen, MD Icahn School of Medicine at Mount Sinai
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Responsible Party: Amir Steinberg, Assistant Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT03219359    
Other Study ID Numbers: GCO 17-0378
First Posted: July 17, 2017    Key Record Dates
Last Update Posted: August 25, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amir Steinberg, Icahn School of Medicine at Mount Sinai:
IBD
Inflammatory Bowel Diseases
Gastroenteritis
Crohn's disease
Colitis
Vedolizumab
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Methylprednisolone
Cyclophosphamide
Vedolizumab
Thymoglobulin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents