High-dose Cyclophosphamide for Severe Refractory Crohn Disease
Primary Purpose
Crohn's Disease, Crohn Disease
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
High-dose Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease
Eligibility Criteria
Inclusion Criteria:
- ≥ 18 years of age, males and females will be eligible
- Moderate to severe Crohn's Disease (CD) with CDAI > 220, in addition to evidence of ulceration on ileocolonoscopy or active disease on small bowel imaging (in patients with an ostomy, CDAI criteria do not apply)
- Disease progression (primary or secondary non-responder, or reaction to) to at least one anti-tumor necrosis factor (TNF) agent (infliximab, adalimumab, certolizumab pegol), and additionally had disease progression despite one of the following immunosuppressant drugs: azathioprine, 6-mercaptopurine, methotrexate, cyclosporine, natalizumab, vedolizumab
- Willingness to participate in a clinical trial
- Approval by Enrollment Panel, who will collectively decide on the appropriateness of possible study study participants
Exclusion Criteria:
- Pregnant or nursing women
- Sexually active men and women who do not agree to use effective means of birth control during treatment period
- Evidence of primarily fibrostenosing disease without active inflammatory disease on disease staging
- Co-morbid conditions including cardiac disease with an ejection fraction of < 45%, chronic renal failure with serum creatinine > 2.0, liver disease with total bilirubin > 2.0, (excluding hyperbilirubinemia secondary to Gilbert's disease) or transaminitis > 3x upper limit of normal.
- History of serious allergic reaction to cyclophosphamide
- History of malignancy in the last 5 years (excluding non-melanomatous skin cancers)
- Patients who are pre-terminal
- Toxic megacolon
- Active infection
- White blood cell count < 3000 cells/ul, platelets < 100K / ul, hemoglobin < 10.0 g/dL
- Any use of thiopurines, methotrexate or anti-TNF agents in the previous four weeks prior to treatment
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
High-dose Cyclophosphamide
Arm Description
High-dose Cyclophosphamide
Outcomes
Primary Outcome Measures
Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol
Tablulation of serious adverse events associate with the HDC protocol
Secondary Outcome Measures
HDC-Induced Steroid-free remission
To determine if HDC therapy can induce and maintain a steroid-free clinical remission (defined as CDAI<150) at 12 and 52 weeks. Applies to patients without an existing ostomy.
HDC-Induced Mucosal Healing
To determine if HDC therapy can induce sustained mucosal healing defined as absence of ulcers on colonoscopy
Improvement in patient reported quality of life
To determine if HDC can lead to improvement in inflammatory bowel disease questionnaire scores at weeks 12 and 52
Molecular Mechanisms of High-dose Cyclophosphamide (HiCy) Therapy
To investigate the molecular mechanisms by which HiCy therapy works by analyzing the effects of HiCy on the levels of serum cytokines (using multiplex ELISA), and correlate the data with clinical activity and treatment response.
Full Information
NCT ID
NCT01836289
First Posted
April 17, 2013
Last Updated
August 9, 2018
Sponsor
Johns Hopkins University
1. Study Identification
Unique Protocol Identification Number
NCT01836289
Brief Title
High-dose Cyclophosphamide for Severe Refractory Crohn Disease
Official Title
High-dose Cyclophosphamide for Severe Refractory Crohn Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Too difficult to recruit given new Crohn's medications approved
Study Start Date
March 2015 (undefined)
Primary Completion Date
March 2018 (Anticipated)
Study Completion Date
March 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This research is being done to see if people with Crohn's disease who receive high-dose cyclophosphamide have an improvement of their disease, how long the benefit may last, and how safe cyclophosphamide is. This study is for patient with medically refractory disease that is not easily amenable to surgery.
Cyclophosphamide is an FDA-approved chemotherapy medication that is also frequently used to treat autoimmune illness; use of cyclophosphamide for autoimmune disease is not approved by the FDA. An autoimmune illness is when the immune system mistakenly attacks self, targeting the cells, tissues, and organs of a person's own body. There are many different autoimmune diseases and they can each affect the body is different ways. Crohn's disease is an autoimmune disease that primarily affects the small and large intestines. High dose-cyclophosphamide has been successfully used to treat Crohn's, primarily as part of a conditioning regimen for autologous stem cell transplantation. However, this therapy is limited in Crohn's because of it's serious infectious risks. This current study involves using high-dose cyclophosphamide without need for stem cell transplantation. This appears to be a safer approach in other autoimmune illnesses that have been studied.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease, Crohn Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High-dose Cyclophosphamide
Arm Type
Experimental
Arm Description
High-dose Cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
High-dose Cyclophosphamide
Other Intervention Name(s)
Endoxan®, Cytoxan®, CTX, Neosar®, Procytox®, Revimmune™
Primary Outcome Measure Information:
Title
Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol
Description
Tablulation of serious adverse events associate with the HDC protocol
Time Frame
3 Years
Secondary Outcome Measure Information:
Title
HDC-Induced Steroid-free remission
Description
To determine if HDC therapy can induce and maintain a steroid-free clinical remission (defined as CDAI<150) at 12 and 52 weeks. Applies to patients without an existing ostomy.
Time Frame
3 Years
Title
HDC-Induced Mucosal Healing
Description
To determine if HDC therapy can induce sustained mucosal healing defined as absence of ulcers on colonoscopy
Time Frame
3 Years
Title
Improvement in patient reported quality of life
Description
To determine if HDC can lead to improvement in inflammatory bowel disease questionnaire scores at weeks 12 and 52
Time Frame
3 years
Title
Molecular Mechanisms of High-dose Cyclophosphamide (HiCy) Therapy
Description
To investigate the molecular mechanisms by which HiCy therapy works by analyzing the effects of HiCy on the levels of serum cytokines (using multiplex ELISA), and correlate the data with clinical activity and treatment response.
Time Frame
3 Years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥ 18 years of age, males and females will be eligible
Moderate to severe Crohn's Disease (CD) with CDAI > 220, in addition to evidence of ulceration on ileocolonoscopy or active disease on small bowel imaging (in patients with an ostomy, CDAI criteria do not apply)
Disease progression (primary or secondary non-responder, or reaction to) to at least one anti-tumor necrosis factor (TNF) agent (infliximab, adalimumab, certolizumab pegol), and additionally had disease progression despite one of the following immunosuppressant drugs: azathioprine, 6-mercaptopurine, methotrexate, cyclosporine, natalizumab, vedolizumab
Willingness to participate in a clinical trial
Approval by Enrollment Panel, who will collectively decide on the appropriateness of possible study study participants
Exclusion Criteria:
Pregnant or nursing women
Sexually active men and women who do not agree to use effective means of birth control during treatment period
Evidence of primarily fibrostenosing disease without active inflammatory disease on disease staging
Co-morbid conditions including cardiac disease with an ejection fraction of < 45%, chronic renal failure with serum creatinine > 2.0, liver disease with total bilirubin > 2.0, (excluding hyperbilirubinemia secondary to Gilbert's disease) or transaminitis > 3x upper limit of normal.
History of serious allergic reaction to cyclophosphamide
History of malignancy in the last 5 years (excluding non-melanomatous skin cancers)
Patients who are pre-terminal
Toxic megacolon
Active infection
White blood cell count < 3000 cells/ul, platelets < 100K / ul, hemoglobin < 10.0 g/dL
Any use of thiopurines, methotrexate or anti-TNF agents in the previous four weeks prior to treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark G. Lazarev, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
High-dose Cyclophosphamide for Severe Refractory Crohn Disease
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