Crohn's DiseasePhase 1/2NCT01836289
High-dose Cyclophosphamide for Severe Refractory Crohn Disease
A Phase 1/2 study testing High-dose Cyclophosphamide in people with Crohn's Disease and Crohn Disease, run by Johns Hopkins University.
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Crohn's Disease, Crohn Disease
- What is being tested?
- High-dose Cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2015to Mar 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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
Who cannot join
- 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)
Show all 11Show fewer
- 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
About this study
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
- Being tested
- High-dose Cyclophosphamide
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose CyclophosphamideDrug
Also called Endoxan®, Cytoxan®, CTX, Neosar®
| Study group | Role | What they receive |
|---|---|---|
| High-dose Cyclophosphamide | Experimental | High-dose Cyclophosphamide Receives: Drug: High-dose Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol
Tablulation of serious adverse events associate with the HDC protocol
Measured: 3 Years
Secondary outcomes (4)
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.
Measured: 3 Years
HDC-Induced Mucosal Healing
To determine if HDC therapy can induce sustained mucosal healing defined as absence of ulcers on colonoscopy
Measured: 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
Measured: 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.
Measured: 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2013 (estimated)
- Study startMar 2015
- Primary completionMar 2018 (estimated)
- Study completionMar 2018 (estimated)
Why it stopped: Too difficult to recruit given new Crohn's medications approved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark G. Lazarev, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01836289
- Sponsor's protocol ID
- NA_00052668
- Status last verified
- Aug 2018
- First submitted
- 17 Apr 2013
- Last updated
- 13 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-dose Cyclophosphamide for Severe Refractory Crohn Disease
- ClinicalTrials.gov ID
- NCT01836289
- Acronym / sponsor ID
- NA_00052668
- Conditions
- Crohn's Disease, Crohn Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Too difficult to recruit given new Crohn's medications approved
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Mar 2018 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 19 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High-dose Cyclophosphamide | Experimental | Drug: High-dose CyclophosphamideHigh-dose Cyclophosphamide |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- ≥ 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-dose CyclophosphamideAlso: Endoxan®, Cytoxan®, CTX, Neosar® | Drug | High-dose Cyclophosphamide |
Primary outcome
Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol
Time frame: 3 Years
Tablulation of serious adverse events associate with the HDC protocol
4 secondary outcomes
HDC-Induced Steroid-free remission
Time frame: 3 Years
HDC-Induced Mucosal Healing
Time frame: 3 Years
Improvement in patient reported quality of life
Time frame: 3 years
Molecular Mechanisms of High-dose Cyclophosphamide (HiCy) Therapy
Time frame: 3 Years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2018.
Related trials for Crohn's Disease
RecruitingPhase 3
A Study to Assess the Pharmacokinetics, Effectiveness and Safety of Afimkibart for Induction and Maintenance Therapy in Children With Moderately to Severely Active Crohn's Disease
Moderately to Severely Active Crohns Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
Not yet recruitingPhase 2
Oral N-acetylglucosamine in Crohn's Disease
Crohns Disease
RecruitingPhase 2
A Phase 2 Study to Evaluate MORF-057 in Adults With Moderately to Severely Active Crohn's Disease
Inflammatory Bowel Diseases, Crohn's Disease
Not yet recruiting
Effects of Different Physical Activity Strategies on Disease Activity of IBD Patients
Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark G. Lazarev, MD principal investigator
Johns Hopkins University
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing High-dose Cyclophosphamide in people with Crohn's Disease and Crohn Disease, run by Johns Hopkins University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol (time frame: 3 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2018.