Stem Cell Transplantation in Crohn's Disease

Registration Number
NCT04224558
Lead Sponsor
Cedars-Sinai Medical Center
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 (i...

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 contr...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
15
Inclusion Criteria

  1. Aged 13-28 years are eligible

  2. Confirmed diagnosis of active Crohn's disease:

    1. Diagnosis of Crohn's disease based on typical radiological appearances and / or typical histology at least 6 months prior to screening.
    2. Active disease at the time of registration to the trial, defined as

    i) PCDAI > 30, and ii) Two of the following:

    1. elevated CRP
    2. endoscopic evidence of active disease confirmed by histology
    3. clear evidence of active small bowel Crohn's disease on CT or MR enterography.

  3. 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.

  4. Current problems unsuitable for surgery or patient at risk for developing short bowel syndrome.

  5. Accepted by a majority of the members of the combined IBD Center as an appropriate candidate (see Selection description below).

  6. Informed consent

    1. Prepared to undergo additional study procedures as per trial schedule
    2. Patient has undergone intensive counseling about risks
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Exclusion Criteria

  1. Pregnancy or unwillingness to use adequate contraception during the study, in women of childbearing age. Unwillingness of using appropriate contraceptive measures in males.

  2. Concomitant severe disease

    1. renal: creatinine clearance < 30 mL/min (measured or estimated)
    2. 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
    3. pulmonary: diffusion capacity <40%
    4. psychiatric disorders including active drug or alcohol abuse
    5. concurrent or recent history of malignant disease (excluding non-melanoma skin cancer)
    6. uncontrolled hypertension, defined as resting systolic blood pressure ≥ 140 and/or resting diastolic pressure ≥ 90 despite at least 2 anti-hypertensive agents.
    7. any infection with HIV, HTLV-1 or 2, hepatitis viruses, or any other infection the investigators consider a contraindication to participation.
    8. other chronic disease causing significant organ failure.

  3. Infection or risk thereof:

    1. Current clinical relevant abscess or significant active infection.
    2. 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.
    3. History of tuberculosis or at current increased risk of tuberculosis
    4. Quantiferon Gold test result or other investigations that the investigators regard as evidence of active tuberculosis.
    5. Abnormal chest X-ray (CXR) consistent with active infection or neoplasm.

  1. Significant malnutrition: Body Mass Index (BMI) ≤ 18, serum albumin < 20 g/l.

  2. 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.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
HSCT after mobilization and conditioningPeripheral Blood Stem Cell InfusionMobilization 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
HSCT after mobilization and conditioningCytoxanMobilization 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
HSCT after mobilization and conditioninglymphocyte immune globulinMobilization 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
HSCT after mobilization and conditioningApheresis catheter placementMobilization 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
HSCT after mobilization and conditioningLeukapheresisMobilization 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
HSCT after mobilization and conditioningMesnaMobilization 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
HSCT after mobilization and conditioningCyclophosphamideMobilization 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
HSCT after mobilization and conditioningFilgrastimMobilization 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
HSCT after mobilization and conditioningMethylprednisoloneMobilization 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
HSCT after mobilization and conditioningFludarabineMobilization 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
HSCT after mobilization and conditioningDiphenhydramineMobilization 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
HSCT after mobilization and conditioningAcetaminophenMobilization 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
HSCT after mobilization and conditioninganti-thymocyte globulin (rabbit)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
Primary Outcome Measures
NameTimeMethod
Change in mucosal healingChange 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...

Change in erythrocyte sedimentation rate (SED rate)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 concentrationChange 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)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]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 ComplicationsUp 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 remissionUp 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...

Secondary Outcome Measures
NameTimeMethod
Change in quality of life0, 2, 4, 6, 12 and 24 months post HSCT

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 (...

Change in school and work productivity0, 2, 4, 6, 12 and 24 months post HSCT

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 impair...

Change in thymopoiesis after HSCT0, 2, 4, 6, 12 and 24 months post 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.

Change in T-cell repertoire after HSCT using spectratyping0, 2, 4, 6, 12 and 24 months post HSCT

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...

Trial Locations

Locations (1)

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

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