High-dose Cyclophosphamide for Severe Refractory Crohn Disease

Crohn's Disease Clinical Trial

Official title:

High-dose Cyclophosphamide for Severe Refractory Crohn Disease

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01836289
• Other study ID #: NA_00052668
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: March 2015
• Est. completion date: March 2018

Study information

• Verified date: August 2018
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• High-dose Cyclophosphamide

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol	Tablulation of serious adverse events associate with the HDC protocol	3 Years
Secondary	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.	3 Years
Secondary	HDC-Induced Mucosal Healing	To determine if HDC therapy can induce sustained mucosal healing defined as absence of ulcers on colonoscopy	3 Years
Secondary	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	3 years
Secondary	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.	3 Years