Stem Cell Transplantation in Crohn's Disease

NCT04224558 | Recruiting Phase 1 FDA Drug

• 1 other identifier: Pro00051458
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (7)

• 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.

  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)

  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

  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)

  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)

  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.

  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.

  Up to 24 months post HSCT

Secondary Outcomes (4)

• Change in quality of life

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

• Change in school and work productivity

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

• Change in thymopoiesis after HSCT

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

• Change in T-cell repertoire after HSCT using spectratyping

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

Study Arms (1)

HSCT after mobilization and conditioning

EXPERIMENTAL

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

Interventions

Diphenhydramine DRUG

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

Also known as: Benadryl

HSCT after mobilization and conditioning

anti-thymocyte globulin (rabbit) DRUG

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

HSCT after mobilization and conditioning

lymphocyte immune globulin DRUG

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

HSCT after mobilization and conditioning

Peripheral Blood Stem Cell Infusion BIOLOGICAL

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

HSCT after mobilization and conditioning

Cytoxan DRUG

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

HSCT after mobilization and conditioning

Mesna DRUG

Stem Cell Mobilization: Infused according to institutional guidelines; Post-PBSC Infusion Conditioning: Mesna provided with Cytoxan according to institutional protocol.

Also known as: Mesnex

HSCT after mobilization and conditioning

Cyclophosphamide DRUG

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

HSCT after mobilization and conditioning

Filgrastim DRUG

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

HSCT after mobilization and conditioning

Apheresis catheter placement PROCEDURE

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

HSCT after mobilization and conditioning

Leukapheresis PROCEDURE

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.

HSCT after mobilization and conditioning

Fludarabine DRUG

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

Also known as: Fludara

HSCT after mobilization and conditioning

Methylprednisolone DRUG

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

Also known as: solu-medrol

HSCT after mobilization and conditioning

Acetaminophen DRUG

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

Also known as: Tylenol

HSCT after mobilization and conditioning

Eligibility Criteria

• Age: 13 Years - 28 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

MeSH Terms

Conditions

Crohn Disease

Interventions

Mesna; Cyclophosphamide; Filgrastim; Leukapheresis; fludarabine; fludarabine phosphate; Methylprednisolone; Methylprednisolone Hemisuccinate; Diphenhydramine; Acetaminophen; Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethylamines; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Acetanilides; Anilides; Amides; Aniline Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• David Ziring, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Ziring, MD

CONTACT

310-423-7100; david.ziring@cshs.org

Yvette Gonzales, MBA

CONTACT

310-423-4072; Yvette.Gonzales@cshs.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director, Pediatric IBD Center

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: January 13, 2020
• Study Start: November 15, 2019
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)