High-dose Cyclophosphamide for Severe Refractory Crohn Disease

NCT01836289 | Withdrawn Phase 1 DMC

• 1 other identifier: NA_00052668
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Crohn's Disease; Crohn Disease

Outcome Measures

Primary Outcomes (1)

• Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol

  Tablulation of serious adverse events associate with the HDC protocol

  3 Years

Secondary Outcomes (4)

• HDC-Induced Steroid-free remission

  3 Years

• HDC-Induced Mucosal Healing

  3 Years

• Improvement in patient reported quality of life

  3 years

• Molecular Mechanisms of High-dose Cyclophosphamide (HiCy) Therapy

  3 Years

Study Arms (1)

High-dose Cyclophosphamide

EXPERIMENTAL

High-dose Cyclophosphamide

Drug: High-dose Cyclophosphamide

Interventions

High-dose Cyclophosphamide DRUG

Also known as: Endoxan®, Cytoxan®, CTX, Neosar®, Procytox®, Revimmune™

High-dose Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead

MeSH Terms

Conditions

Crohn Disease

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Mark G. Lazarev, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 19, 2013
• Study Start: March 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: August 13, 2018

Record last verified: 2018-08