NCT04224558 · Cedars-Sinai Medical Center
Stem Cell Transplantation in Crohn's Disease
What this study is about
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).
View original scientific description
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.
Interventions
DRUG
Mesna
Stem Cell Mobilization: Infused according to institutional guidelines; Post-PBSC Infusion Conditioning: Mesna provided with Cytoxan according to institutional protocol.
DRUG
Cyclophosphamide
Stem Cell Mobilization: Cyclophosphamide (CY) infused intravenously over 1 hour: 50 mg/kg (25 mg/kg/day on 2 consecutive days)
DRUG
Filgrastim
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
PROCEDURE
Apheresis catheter placement
Subjects will require placement of an Apheresis catheter by Intervention Radiologists on the day of collection of stem cells.
PROCEDURE
Leukapheresis
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.
DRUG
Fludarabine
Preparative/Conditioning Regime Fludarabine given as 30 mg/m2 per dose x 4 days, beginning on day -6.
DRUG
Methylprednisolone
Preparative/Conditioning Regime r-ATG pre-medication according to institutional guidelines
DRUG
Diphenhydramine
Preparative/Conditioning Regime r-ATG premedication according to institutional guidelines
DRUG
Acetaminophen
Preparative/Conditioning Regime r-ATG premedication according to institutional guidlines
DRUG
anti-thymocyte globulin (rabbit)
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.
DRUG
lymphocyte immune globulin
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.
BIOLOGICAL
Peripheral Blood Stem Cell Infusion
PBSC (peripheral blood stem cell) infusion on day 0 as per institutional guidelines.
DRUG
Cytoxan
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.
Primary outcome measures
Change in mucosal healing
Time frame: Change from pre-HSCT (baseline) to 6 months and 12 months post HSCT
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.
Change in erythrocyte sedimentation rate (SED rate)
Time frame: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT
Change in SED rate (mm/hour)
Change in fecal calprotectin concentration
Time frame: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT
Change in fecal calprotectin concentration
Change in C reactive protein (CRP)
Time frame: Change from pre-HSCT (baseline) to 2, 4, 6, 12, and 24 months post HSCT
Change in C reactive protein (CRP)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Up to 24 months post HSCT
Number of treatment-emergent adverse events (including death (transplant related mortality, TRM) and severe toxicity (≥ grade 3 toxicity; NCI Toxicity Criteria version 4.0)
Incidence of HSCT Related Complications
Time frame: Up to 24 months post HSCT
The incidence of HSCT related complications, i.e. viral reactivations (CMV, Adenovirus, EBV, BK virus) or fungal infections.
Change in clinical measures of sustained remission
Time frame: Up to 24 months post HSCT
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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 i) PCDAI \> 30, and ii) Two of the following:
- elevated CRP
- 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
Exclusion criteria
- 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
- 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.
Where
- Los Angeles, California
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Feb 20, 2026 · Source of record for eligibility and locations