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High-dose Cyclophosphamide for Severe Refractory Crohn Disease

This study is currently recruiting participants.
Verified March 2015 by Mark Lazarev, MD, Johns Hopkins University
Sponsor:
ClinicalTrials.gov Identifier:
NCT01836289
First Posted: April 19, 2013
Last Update Posted: March 3, 2015
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.
Information provided by (Responsible Party):
Mark Lazarev, MD, Johns Hopkins University
  Purpose

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.


Condition Intervention Phase
Crohn's Disease Crohn Disease Drug: High-dose Cyclophosphamide Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High-dose Cyclophosphamide for Severe Refractory Crohn Disease

Resource links provided by NLM:


Further study details as provided by Mark Lazarev, MD, Johns Hopkins University:

Primary Outcome Measures:
  • Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol [ Time Frame: 3 Years ]
    Tablulation of serious adverse events associate with the HDC protocol


Secondary Outcome Measures:
  • HDC-Induced Steroid-free remission [ Time Frame: 3 Years ]
    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 [ Time Frame: 3 Years ]
    To determine if HDC therapy can induce sustained mucosal healing defined as absence of ulcers on colonoscopy

  • Improvement in patient reported quality of life [ Time Frame: 3 years ]
    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 [ Time Frame: 3 Years ]
    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.


Estimated Enrollment: 10
Study Start Date: March 2015
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High-dose Cyclophosphamide
High-dose Cyclophosphamide
Drug: High-dose Cyclophosphamide
Other Names:
  • Endoxan®
  • Cytoxan®
  • CTX
  • Neosar®
  • Procytox®
  • Revimmune™

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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): NCT01836289


Contacts
Contact: Mark G. lazarev, MD 410.502-3147 mlazare1@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Medical Institutions Recruiting
Baltimore, Maryland, United States, 21205
Contact: Mark G. lazarev, MD    410-502-3147    mlazare1@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Mark G. Lazarev, MD Johns Hopkins University
  More Information

Responsible Party: Mark Lazarev, MD, Assistant Professor of Medicine, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01836289     History of Changes
Other Study ID Numbers: NA_00052668
First Submitted: April 17, 2013
First Posted: April 19, 2013
Last Update Posted: March 3, 2015
Last Verified: March 2015

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists


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