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Crohn DiseasePhase 1/2NCT04224558

Stem Cell Transplantation in Crohn's Disease

A Phase 1/2 study testing Mesna, Cyclophosphamide and Filgrastim in people with Crohn Disease, run by Cedars-Sinai Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Unfortunately, some patients with Crohn's disease (CD) fail to respond to the best clinical treatments and some only experience temporary benefit. For severe Crohn's disease, there is an experimental treatment called "high dose immunoablation" followed by autologous hematopoietic stem cell transplantation (HSCT). Read more about this study

Who is it for?
Ages 13 to 28 years
Conditions the study is for
Crohn Disease
What is being tested?
Mesna, Cyclophosphamide and Filgrastim
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
15 Nov 2019to 30 Sep 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 13 to 28 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Aged 13-28 years are eligible
  • Confirmed diagnosis of active Crohn's disease:
  • Diagnosis of Crohn's disease based on typical radiological appearances and / or typical histology at least 6 months prior to screening.
  • Active disease at the time of registration to the trial, defined as
  • PCDAI > 30, and ii) Two of the following:
  • elevated CRP
Show all 14Show fewer
  • endoscopic evidence of active disease confirmed by histology
  • clear evidence of active small bowel Crohn's disease on CT or MR enterography.
  • Unsatisfactory course despite 3 immunosuppressive agents (usually azathioprine, methotrexate and infliximab, adalimumab and/or certolizumab) in addition to corticosteroids. Patients should have relapsing disease (i.e. 1 exacerbation/year) despite thiopurines, methotrexate and/or infliximab/adalimumab/certolizumab maintenance therapy or clear demonstration of intolerance / toxicity to these drugs.
  • Current problems unsuitable for surgery or patient at risk for developing short bowel syndrome.
  • Accepted by a majority of the members of the combined IBD Center as an appropriate candidate (see Selection description below).
  • Informed consent
  • Prepared to undergo additional study procedures as per trial schedule
  • Patient has undergone intensive counseling about risks

Who cannot join

  • Pregnancy or unwillingness to use adequate contraception during the study, in women of childbearing age. Unwillingness of using appropriate contraceptive measures in males.
  • Concomitant severe disease
  • renal: creatinine clearance < 30 mL/min (measured or estimated)
  • cardiac: clinical evidence of refractory congestive heart failure; left ventricular ejection fraction < 40% by cardiac echo; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with hemodynamic consequences as evaluated by an experienced echo cardiographer
  • pulmonary: diffusion capacity <40%
  • psychiatric disorders including active drug or alcohol abuse
Show all 18Show fewer
  • concurrent or recent history of malignant disease (excluding non-melanoma skin cancer)
  • uncontrolled hypertension, defined as resting systolic blood pressure ≥ 140 and/or resting diastolic pressure ≥ 90 despite at least 2 anti-hypertensive agents.
  • any infection with HIV, HTLV-1 or 2, hepatitis viruses, or any other infection the investigators consider a contraindication to participation.
  • other chronic disease causing significant organ failure.
  • Infection or risk thereof:
  • Current clinical relevant abscess or significant active infection.
  • Perianal fistula without free drainage. Perianal fistulas is not an exclusion provided there is natural free drainage or a seton suture(s) have been placed.
  • History of tuberculosis or at current increased risk of tuberculosis
  • Quantiferon Gold test result or other investigations that the investigators regard as evidence of active tuberculosis.
  • Abnormal chest X-ray (CXR) consistent with active infection or neoplasm.
  • 6) Significant malnutrition: Body Mass Index (BMI) ≤ 18, serum albumin < 20 g/l.
  • 7) Previous poor compliance. 8) Concurrent enrollment in any other protocol using an investigational drug or hematopoietic growth factor up to four weeks before study entry.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

David Ziring, MD contact

310-423-7100

david.ziring@cshs.org

Yvette Gonzales, MBA contact

310-423-4072

Yvette.Gonzales@cshs.org

United States1 site, 1 recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    David Ziring, MD, 310-423-7100, David.Ziring@cshs.org

    Yvette Gonzales, MBA, 310-423-4072, Yvette.Gonzales@cshs.org

    Recruiting

Other trials in United States

About this study

Official title: Autologous Hematopoietic Stem Cell Transplantation for Refractory Crohn's Disease

Unfortunately, some patients with Crohn's disease (CD) fail to respond to the best clinical treatments and some only experience temporary benefit. For severe Crohn's disease, there is an experimental treatment called "high dose immunoablation" followed by autologous hematopoietic stem cell transplantation (HSCT). This study removes over active lymphocytes (immunoablation) and replaces them using blood stem cells that have been taken from the patient's own body. The aim of the study is to reset or reprogram the patient's immune system to its state prior to diagnosis.

Read the detailed description

The treatment of Crohn's disease has proven to be quite efficacious in the majority of patients with the timely use of combination therapies for remission induction (corticosteroids and/or biologics) and maintenance of disease control (immunosuppressives and/or biologics). However, a proportion of patients fail to achieve complete and long term disease control and often require multiple intestinal surgeries with a risk of developing short bowel syndrome. Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system has been proposed as an alternative strategy to induce long term disease control in this high-risk population. It has been demonstrated that despite the potential toxicity and morbidity associated with the procedure, the benefit-risk ratio is favorable. Hence, the investigators propose to offer HSCT to selected CD patients and to study mechanisms of reducing T cell autoreactivity which will hopefully lead to more focused therapeutic approaches in the future.

This is an open-label, non-randomized, non-blinded, prospective study in therapeutic refractory Crohn's patients, failing conventional therapy.

The primary objective is to evaluate the safety and potential clinical benefit of lymphoablation followed by autologous HSCT rescue in therapy refractory CD. Death (transplant-related mortality, TRM) and severe toxicity (≥ grade 3 toxicity; NCI Toxicity Criteria version 4.0) within the first 6 months after HSCT will be monitored to meet this end-point.

SECONDARY OBJECTIVES

  1. To evaluate the incidence of HSCT related complications, i.e. viral reactivations (CMV, Adenovirus, EBV, BK virus) or fungal infections.
  2. To evaluate the impact of HSCT on quality of life and school productivity.
  3. To elucidate the underlying mechanism involved in the observed benefit of HSCT on CD.

First, the safety will be evaluated by the amount of related adverse events. All adverse events will be recorded in a standardized way and their relationship to the study protocol will be assessed at various short and long term time points.

Second, to determine clinical benefit, the percentage of patients in sustained disease remission at 0, 2, 4, 6, 12 and 24 months post HSCT will be determined. Sustained disease remission is defined as a Crohn's Disease Activity Index (CDAI) < 150 without the use of corticosteroids. In addition, mucosal healing will be assessed during ileocolonoscopy at 6 and 12 months following HSCT using the CD endoscopic index (SES).

SECONDARY ENDPOINTS

  • Change in Crohn's disease endoscopic index after 6 and 12 months.
Conditions
Crohn Disease
Being tested
Mesna, Cyclophosphamide, Filgrastim, Apheresis catheter placement, Leukapheresis
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MesnaDrug

    Also called Mesnex

    Stem Cell Mobilization: Infused according to institutional guidelines;

    Post-PBSC Infusion Conditioning: Mesna provided with Cytoxan according to institutional protocol.

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

    Stem Cell Mobilization:

    Cyclophosphamide (CY) infused intravenously over 1 hour: 50 mg/kg (25 mg/kg/day on 2 consecutive days)

  • FilgrastimDrug

    Also called Neupogen, Granix

    Stem Cell Mobilization: Filgrastim (G-CSF) 10 mcg/kg SC will start 5 days after the last dose of CY and will end the day before the last leukapheresis;

    Post-PBSC Infusion Conditioning: Filgrastim administered intravenously 5 mcg/kg IV starting day + 5, continue until ANC of >1000/μL

  • Apheresis catheter placementProcedure or surgery

    Subjects will require placement of an Apheresis catheter by Intervention Radiologists on the day of collection of stem cells.

  • LeukapheresisProcedure or surgery

    Leukapheresis will be performed on a continuous flow separator machine according to institutional guidelines to target 3-8 x 10^6 CD34+ cells/kg body weight.

  • FludarabineDrug

    Also called Fludara

    Preparative/Conditioning Regime Fludarabine given as 30 mg/m2 per dose x 4 days, beginning on day -6.

  • MethylprednisoloneDrug

    Also called solu-medrol

    Preparative/Conditioning Regime r-ATG pre-medication according to institutional guidelines

  • DiphenhydramineDrug

    Also called Benadryl

    Preparative/Conditioning Regime r-ATG premedication according to institutional guidelines

  • AcetaminophenDrug

    Also called Tylenol

    Preparative/Conditioning Regime r-ATG premedication according to institutional guidlines

  • anti-thymocyte globulin (rabbit)Drug

    Also called thymoglobulin

    Preparative/Conditioning Regime r-ATG administered intravenously: 2.5 mg/kg/dose IV over 6 hours on specified days (day -6,-4,-2); ); total 3 doses=7.5 mg/kg.

  • lymphocyte immune globulinDrug

    Also called ATGAM

    Preparative/Conditioning Regime In patients who develop severe allergic reactions to rATG (Thymoglobulin), it may be substituted by horse ATG (hATG, ATGAM, Pharmacia \& Upjohn, Kalamazoo, MI). The recommended dose of hATG is 25 mg/kg/day for 3 doses.

  • Peripheral Blood Stem Cell InfusionBiological

    PBSC (peripheral blood stem cell) infusion on day 0 as per institutional guidelines.

  • CytoxanDrug

    Also called Cyclophosphamide

    Post-PBSC Infusion Conditioning Cytoxan infused intravenously: 50mg/kg/day x 2 days. Infused over 2 hours with adequate hydration or according to institutional guidelines.

Study groups in NCT04224558
Study groupRoleWhat they receive
HSCT after mobilization and conditioningExperimentalMobilization and leukopheresis allow for stem cell harvest. Then conditioning is provided prior to stem cell transplantation, followed by post-transplant conditioning. Interventions include: 1. Stem cell mobilization 2. Leukopheresis 3. Preparative regimen 4. Peripheral blood stem cell infusion 5. Post-PBSC infusion conditioning
Receives: Drug: Mesna; Drug: Cyclophosphamide; Drug: Filgrastim; Procedure: Apheresis catheter placement; Procedure: Leukapheresis; Drug: Fludarabine; Drug: Methylprednisolone; Drug: Diphenhydramine; Drug: Acetaminophen; Drug: anti-thymocyte globulin (rabbit); Drug: lymphocyte immune globulin; Biological: Peripheral Blood Stem Cell Infusion; Drug: Cytoxan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in mucosal healing

    Change mucosal healing as determined by the simple endoscopic score for crohn's disease (SES-CD). The SES-CD assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. Each are measured on a scale of 0-3 and are summed to create a total score. For total score, 0-2 indicates remission, 3-6 indicates mild endoscopic activity, 7-15 indicates moderate endoscopic activity, and > 15 indicates severe endoscopic activity.

    Measured: Change from pre-HSCT (baseline) to 6 months and 12 months post HSCT

  2. Change in erythrocyte sedimentation rate (SED rate)

    Change in SED rate (mm/hour)

    Measured: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT

  3. Change in fecal calprotectin concentration

    Change in fecal calprotectin concentration

    Measured: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT

  4. Change in C reactive protein (CRP)

    Change in C reactive protein (CRP)

    Measured: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT

  5. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Number of treatment-emergent adverse events (including death (transplant related mortality, TRM) and severe toxicity (≥ grade 3 toxicity; NCI Toxicity Criteria version 4.0)

    Measured: Up to 24 months post HSCT

  6. Incidence of HSCT Related Complications

    The incidence of HSCT related complications, i.e. viral reactivations (CMV, Adenovirus, EBV, BK virus) or fungal infections.

    Measured: Up to 24 months post HSCT

  7. Change in clinical measures of sustained remission

    Change in CDAI score (Crohn's Disease Activity Index). The CDAI measure the signs, symptoms, and history of Crohn's Disease based on the past 7 days. The index measures abdominal pain, stools per day, general wellbeing, HCT, ESR, Albumin, height, weight, abdominal exam, perirectal disease, and extra-intestinal manifestations each scaled between 0-10. The sum of these measures creates a total score between 0-100 with the higher score representative of more disease activity.

    Measured: Up to 24 months post HSCT

Secondary outcomes (4)

  1. Change in quality of life

    Change in score on the IMPACT-III Questionnaire (A Quality of Life Questionnaire for Children with Inflammatory Bowel Disease) after HSCT. It is a self-report measure with 35 closed questions encompassing six proposed domains: Bowel Symptoms (7 items), Systemic Symptoms (3 items), Social Functioning (12 items), Body Image (3 items), Treatment/Interventions (3 items), and Emotional Functioning (7 items). The IMPACT-III uses 5-point Likert scale ranging from 1 to 5 for all answers. The outcome score ranges from 35 to 175, with higher scores suggesting better quality of life.

    Measured: 0, 2, 4, 6, 12 and 24 months post HSCT

  2. Change in school and work productivity

    Change in school productivity and activity impairment as determined by the modified Work Productivity and Activity Impairment (WPAI) Index score. The Modified WPAI yield four types of scores: absenteeism (school time missed), presenteeism (impairement at school), school productivity (overall work impairment/absenteeism plus presenteeism), and activity impairement. WPAI outcomes are expressed as impairement percentages, with higher numbers indicating greater impairement and less productivity.

    Measured: 0, 2, 4, 6, 12 and 24 months post HSCT

  3. Change in thymopoiesis after HSCT

    the amount of T-cell receptor excision circles (TREC) will be determined. TRECs are excision circles of DNA excised during the process of T cell receptor (TCR) rearrangement. Since these TRECs do not replicate during cell division, they can also be a measure for recent thymic emigrants.

    Measured: 0, 2, 4, 6, 12 and 24 months post HSCT

  4. Change in T-cell repertoire after HSCT using spectratyping

    The CDR3 (complement determining region) of the TCRβ chain is the most variable region of the TCR and is generated by recombination of the variable, diversity and joining region of the DNA. The length of this region differs between different T-cell clones due to nucleotide transferases or removed nucleotides during recombination, and the variability of these lengths can be used to estimate thymic diversity. This variability can be determined by electrophoresis, after amplification of this region by PCR.

    Measured: 0, 2, 4, 6, 12 and 24 months post HSCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2020
  2. Study start15 Nov 2019
  3. Primary completion30 Sep 2027 (estimated)
  4. Study completion30 Sep 2027 (estimated)

Resources

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
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04224558
Sponsor's protocol ID
Pro00051458
Status last verified
Feb 2026
First submitted
4 Apr 2018
Last updated
20 Feb 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Mesna, Cyclophosphamide and Filgrastim in people with Crohn Disease, run by Cedars-Sinai Medical Center at 1 site in United States.

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 14 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Ziring, MD (310-423-7100, david.ziring@cshs.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in mucosal healing (time frame: Change from pre-HSCT (baseline) to 6 months and 12 months post HSCT). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04224558.

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 20 Feb 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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