A Phase 1/2 interventional study of Mesna and Cyclophosphamide in Crohn Disease, sponsored by Cedars-Sinai Medical Center. Recruiting at 1 site in United States. Open to participants aged 13 Years to 28 Years. Per ClinicalTrials.gov, last updated 2026-02-20.
Sponsored by Cedars-Sinai Medical Center · Phase 1/2, Interventional, and Treatment
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.
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
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.
1,880 studies on the registry are indexed under Crohn Disease; 462 are open to participants now.
This study's planned enrollment of 15 is below the median of 66 across 1,188 interventional studies indexed under Crohn Disease.
Browse Crohn Disease studies →Cedars-Sinai Medical Center is the lead sponsor of 441 studies on the registry; 108 are open to participants now.
Of its 62 completed or terminated interventional studies of FDA-regulated products, 47 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Confirmed diagnosis of active Crohn's disease:
i) PCDAI > 30, and ii) Two of the following:
Informed consent
Exclusion Criteria:
Concomitant severe disease
Infection or risk thereof:
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.
Mobilization 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
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
Stem Cell Mobilization: Infused according to institutional guidelines; Post-PBSC Infusion Conditioning: Mesna provided with Cytoxan according to institutional protocol.
Also known as: Mesnex
Stem Cell Mobilization: Cyclophosphamide (CY) infused intravenously over 1 hour: 50 mg/kg (25 mg/kg/day on 2 consecutive days)
Also known as: Cytoxan, Neosar
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
Also known as: Neupogen, Granix
Subjects will require placement of an Apheresis catheter by Intervention Radiologists on the day of collection of stem cells.
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.
Preparative/Conditioning Regime Fludarabine given as 30 mg/m2 per dose x 4 days, beginning on day -6.
Also known as: Fludara
Preparative/Conditioning Regime r-ATG pre-medication according to institutional guidelines
Also known as: solu-medrol
Preparative/Conditioning Regime r-ATG premedication according to institutional guidelines
Also known as: Benadryl
Preparative/Conditioning Regime r-ATG premedication according to institutional guidlines
Also known as: Tylenol
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.
Also known as: thymoglobulin
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.
Also known as: ATGAM
PBSC (peripheral blood stem cell) infusion on day 0 as per institutional guidelines.
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.
Also known as: Cyclophosphamide
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.
Time frame: Change from pre-HSCT (baseline) to 6 months and 12 months post HSCT
Change in erythrocyte sedimentation rate (SED rate)
Change in SED rate (mm/hour)
Time frame: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT
Change in fecal calprotectin concentration
Change in fecal calprotectin concentration
Time frame: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT
Change in C reactive protein (CRP)
Change in C reactive protein (CRP)
Time frame: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT
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)
Time frame: Up to 24 months post HSCT
Incidence of HSCT Related Complications
The incidence of HSCT related complications, i.e. viral reactivations (CMV, Adenovirus, EBV, BK virus) or fungal infections.
Time frame: Up to 24 months post HSCT
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.
Time frame: Up to 24 months post HSCT
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.
Time frame: 0, 2, 4, 6, 12 and 24 months post HSCT
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.
Time frame: 0, 2, 4, 6, 12 and 24 months post HSCT
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.
Time frame: 0, 2, 4, 6, 12 and 24 months post HSCT
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.
Time frame: 0, 2, 4, 6, 12 and 24 months post HSCT
Plan to share: No
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