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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Withdrawn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
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Crohn's Disease

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    April 17, 2013
    Last Updated
    August 9, 2018
    Sponsor
    Johns Hopkins University
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    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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