High-dose Cyclophosphamide for Severe Refractory Crohn Disease

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.

Study Overview

• Status: Withdrawn
• Conditions: Crohn's Disease; Crohn Disease
• Intervention / Treatment: Drug: High-dose Cyclophosphamide

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High-dose Cyclophosphamide	Drug: High-dose Cyclophosphamide; Other Names: CTX; Cytoxan®; Neosar®; Endoxan®; Procytox®; Revimmune™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol	Tablulation of serious adverse events associate with the HDC protocol	3 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
HDC-Induced Mucosal Healing	To determine if HDC therapy can induce sustained mucosal healing defined as absence of ulcers on colonoscopy	3 Years
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
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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Mark G. Lazarev, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (ANTICIPATED): March 1, 2018
• Study Completion (ANTICIPATED): March 1, 2018

Study Registration Dates

• First Submitted: April 17, 2013
• First Submitted That Met QC Criteria: April 17, 2013
• First Posted (ESTIMATE): April 19, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: NA_00052668