Clinical trial NCT01836289: High-dose Cyclophosphamide for Severe Refractory Crohn Disease
Official title: High-dose Cyclophosphamide for Severe Refractory Crohn Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Crohn's Disease
Crohn Disease
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2013-04-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol
timeFrame: 3 Years
Secondary outcomes:
measure: HDC-Induced Steroid-free remission
timeFrame: 3 Years
measure: HDC-Induced Mucosal Healing
timeFrame: 3 Years
measure: Improvement in patient reported quality of life
timeFrame: 3 years
measure: Molecular Mechanisms of High-dose Cyclophosphamide (HiCy) Therapy
timeFrame: 3 Years
Other outcomes:
Locations:
Study officials:
affiliation: Johns Hopkins University
name: Mark G. Lazarev, MD
role: PRINCIPAL_INVESTIGATOR
References: