Crohn's DiseaseAutoChronNCT03000296
Autologous Unselected Hematopoietic Stem Cell Transplantation for Refractory Crohn's Disease
A study testing Autologous Hematopoietic Stem Cell Transplantation in people with Crohn's Disease and Inflammatory Bowel Diseases, run by Beneficência Portuguesa de São Paulo at 1 site in Brazil.
Trial summary
This study evaluates the safety and clinical benefits of a therapeutic approach using the cyclophosphamide (Cy) + thymoglobulin® (ATG) + granulocyte colony-stimulating factor (G-CSF) conditioning regimen followed by autologous hematopoietic stem cell transplantation (HSCT) rescue in the treatment of refractory Crohn's… Read more about this study
- Who is it for?
- Ages 14 to 70 years
- Conditions the study is for
- Crohn's Disease, Inflammatory Bowel Diseases, Gastroenteritis
- What is being tested?
- Autologous Hematopoietic Stem Cell Transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- Oct 2013to Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 14 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age between 14 and 50 years (patients aged 50 - 70 can participate at the principal investigators discretion).
- Confirmed diagnosis of active Crohn's disease:
- Diagnosis of Crohn's disease based on typical radiological findingsand or typical histology at least 6 months prior to screening.
- Active disease at the time of registration to the trial, defined as
- Crohn's Disease Activity Index (CDAI) > 150, and ii) Two of the following:
- Harvey Bradshaw Index > 4
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- Endoscopic evidence of active disease confirmed by histology
- Clear evidence of active small bowel Crohn's disease on computed tomography (CT) or magnetic resonance (MR) enterography.
- Unsatisfactory course despite immunosuppressive agents (usually azathioprine, methotrexate and two biologic agents (normally infliximab, adalimumab and/or certolizumab) in addition to corticosteroids. Patients should have relapsing and refractory disease 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.
- 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 multigated radionuclide angiography (MUGA) or 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
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- 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.
- uncontrolled acute or chronic infection with HIV, Human T-lymphotropic virus (HTLV-1 or 2), hepatitis viruses or any other infection the investigators consider a contraindication to participation.
- other chronic disease causing significant organ failure.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Beneficencia Portuguesa
São José do Rio Preto, São Paulo, 15015-750
About this study
This study evaluates the safety and clinical benefits of a therapeutic approach using the cyclophosphamide (Cy) + thymoglobulin® (ATG) + granulocyte colony-stimulating factor (G-CSF) conditioning regimen followed by autologous hematopoietic stem cell transplantation (HSCT) rescue in the treatment of refractory Crohn's disease. Adverse events, and clinical and endoscopic conditions will be assessed at different short and long-term time points.
Read the detailed description
Crohn's disease (CD) is a chronic, refractory inflammatory bowel disease that affects the entire digestive tract associated with intestinal and extra intestinal manifestations or other autoimmune diseases. Conventional therapy for Crohn's disease includes anti-inflammatory, immunosuppressant and/or biologic drugs/corticosteroids. This treatment benefits the majority of patients. 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.
Hematopoietic stem cell transplantation (HSCT) has been proposed to cause lymphoablation and reset of the immune system as an alternative strategy to induce long-term disease control in this high-risk population.
This study enrolled Crohn's disease patients not responsive to conventional therapy.
Initially safety and the clinical outcome will be evaluated. The selected patients will be admitted to the bone marrow transplant (BMT) unit for the mobilization regimen using cyclophosphamide (Cy - 60 mg/kg) and G-CSF (10 mcg/kg/day) from the 5th day after Cy administration until harvesting progenitor cells from peripheral blood by leukapheresis.
After seven days of rest, the conditioning regimen consists of Cy (200 mg/kg total dose for four days), rabbit antithymocyte globulin (6.5 mg/kg total dose for four days) and methylprednisolone (500 mg/day).
The clinical course of patients with refractory Crohn´s disease will be evaluated to determine the efficacy of HSCT as a therapeutic tool including the adverse aspects of the procedure, clinical outcome and quality of life.
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation
- Keywords
- autologous, lymphoablation, hematopoetic stem cell transplant, immune system, Bone marrow transplant
- Medical subject headings
- Crohn Disease, Inflammatory Bowel Diseases, Gastroenteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Bone Marrow Transplantation, Hematopoietic Stem Cell Transplatation
Hematopoietic stem cell transplantation Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system.
| Study group | Role | What they receive |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | High doses immunosuppression Cyclophosphamide (200 mg/kg total dose for four days) and rabbit antithymocyte globulin (6.5 mg/kg total dose for four days) followed by unselected autologous hematopoietic stem cell transplantation rescue. Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of unselected autologous HSCT in refractory Crohn´s disease patients
HHSCT safety will be analyzed by laboratory tests and treatment-related adverse events. Safety will be evaluated by treatment-related adverse events. All adverse events will be recorded in a standardized way and their relationship to the study protocol will be assessed at different short- and long-term time points.
Measured: 12 months
Secondary outcomes (8)
Crohn´s Disease Activity Index (CDAI)
Duration of disease remission, defined as a CDAI ≤ 150, will be assessed at 1, 3, 6, 12 and 24 months after transplant.
Measured: 12 months
CRAIG Crohn´s Severity Score (CSS)
The CRAIG CSS will be assessed at 1, 3, 6, 12 and 24 months after transplant.
Measured: 12 months
Inflammatory Bowel Disease Questionnaire (IBDQ)
The IBDQ will be administered at 1, 3, 6, 12 and 24 months after transplant.
Measured: 24 months
Short Form-36 Health Survey (SF-36)
The SF-36 will be administered at 1, 3, 6, 12 and 24 months after transplant.
Measured: 24 months
Simple Endoscopic Activity Score (SES)
The SES will be assessed at 6, 12 and 24 months after HSCT.
Measured: 24 months
Crohn's Disease Endoscopic Index of Severity (CDEIS)
The CDEIS will be assessed at 6, 12 and 24 months after HSCT.
Measured: 24 months
Rutgeerts endoscopic score
Rutgeerts endoscopic score will be assessed at 6, 12 and 24 months after HSCT.
Measured: 24 months
Harvey & Bradshaw Index (HBI)
The HBI will be assessed at 1, 3, 6, 12 and 24 months after HSCT.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2016 (estimated)
- Study startOct 2013
- Primary completionDec 2017
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beneficência Portuguesa de São Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Milton Artur Ruiz, Beneficência Portuguesa de São Paulo
- Investigators
- Milton A Ruiz, MD, PhD, Principal investigator, Beneficencia Portuguesa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03000296
- Sponsor's protocol ID
- autocrohnproject1
- Acronym
- AutoChron
- Status last verified
- Jan 2021
- First submitted
- 9 Dec 2016
- Last updated
- 15 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The main objective is to observe the safety and clinical benefit of autologous HSCT therapy in refractory patients with Crohn's disease. Evaluation during transplant period and 1, 3, 6, 12 and 24 months post-transplant. Safety be evaluated by the amount of treatment-related adverse events. Record adverse events in a standardized way. Secondary outcome measures will be disease remission: 1, 3, 6, 12 and 24 months post-transplant both clinical and endoscopic remission. The percentage of patients in sustained disease remission at 1, 3, 6, 12 and 24 months post HSCT will be determined. Sustained disease remission is defined as a CDAI \< 150; HBI \<4, CCSI\< 16, without the use of corticosteroids, immunosuppressant or biologic agents. Mucosal healing will be assessed during ileocolonoscopy at 6, 12, and 24 months following HSCT using SES, CDEIS and Rutgeerts endoscopy index. Heath Quality life, Short Form 36 and IBDQ at 1 3 6 12 and 24 months post-Transplant.
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Unselected Hematopoietic Stem Cell Transplantation for Refractory Crohn's Disease
- ClinicalTrials.gov ID
- NCT03000296
- Acronym / sponsor ID
- AutoChron / autocrohnproject1
- Keywords
- autologous, lymphoablation, hematopoetic stem cell transplant, immune system, Bone marrow transplant
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Beneficência Portuguesa de São PauloUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2024 (estimated)
- First posted
- 22 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the safety and clinical benefits of a therapeutic approach using the cyclophosphamide (Cy) + thymoglobulin® (ATG) + granulocyte colony-stimulating factor (G-CSF) conditioning regimen followed by autologous hematopoietic stem cell transplantation (HSCT) rescue in the treatment of refractory Crohn's disease. Adverse events, and clinical and endoscopic conditions will be assessed at different short and long-term time points.
Detailed description
Crohn's disease (CD) is a chronic, refractory inflammatory bowel disease that affects the entire digestive tract associated with intestinal and extra intestinal manifestations or other autoimmune diseases. Conventional therapy for Crohn's disease includes anti-inflammatory, immunosuppressant and/or biologic drugs/corticosteroids. This treatment benefits the majority of patients. 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.
Hematopoietic stem cell transplantation (HSCT) has been proposed to cause lymphoablation and reset of the immune system as an alternative strategy to induce long-term disease control in this high-risk population.
This study enrolled Crohn's disease patients not responsive to conventional therapy.
Initially safety and the clinical outcome will be evaluated. The selected patients will be admitted to the bone marrow transplant (BMT) unit for the mobilization regimen using cyclophosphamide (Cy - 60 mg/kg) and G-CSF (10 mcg/kg/day) from the 5th day after Cy administration until harvesting progenitor cells from peripheral blood by leukapheresis.
After seven days of rest, the conditioning regimen consists of Cy (200 mg/kg total dose for four days), rabbit antithymocyte globulin (6.5 mg/kg total dose for four days) and methylprednisolone (500 mg/day).
The clinical course of patients with refractory Crohn´s disease will be evaluated to determine the efficacy of HSCT as a therapeutic tool including the adverse aspects of the procedure, clinical outcome and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Procedure: Autologous Hematopoietic Stem Cell TransplantationHigh doses immunosuppression Cyclophosphamide (200 mg/kg total dose for four days) and rabbit antithymocyte globulin (6.5 mg/kg total dose for four days) followed by unselected autologous hematopoietic stem cell transplantation rescue. |
Who may qualify
- Ages
- 14 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Age between 14 and 50 years (patients aged 50 - 70 can participate at the principal investigators discretion).
- Confirmed diagnosis of active Crohn's disease:
- Unsatisfactory course despite immunosuppressive agents (usually azathioprine, methotrexate and two biologic agents (normally infliximab, adalimumab and/or certolizumab) in addition to corticosteroids. Patients should have relapsing and refractory disease 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.
- Informed consent:
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Hematopoietic Stem Cell TransplantationAlso: Bone Marrow Transplantation, Hematopoietic Stem Cell TransplatationHematopoietic stem cell transplantation Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system. | Procedure or surgery | Hematopoietic Stem Cell Transplantation |
Primary outcome
Safety of unselected autologous HSCT in refractory Crohn´s disease patients
Time frame: 12 months
HHSCT safety will be analyzed by laboratory tests and treatment-related adverse events. Safety will be evaluated by treatment-related adverse events. All adverse events will be recorded in a standardized way and their relationship to the study protocol will be assessed at different short- and long-term time points.
8 secondary outcomes
Crohn´s Disease Activity Index (CDAI)
Time frame: 12 months
CRAIG Crohn´s Severity Score (CSS)
Time frame: 12 months
Inflammatory Bowel Disease Questionnaire (IBDQ)
Time frame: 24 months
Short Form-36 Health Survey (SF-36)
Time frame: 24 months
Simple Endoscopic Activity Score (SES)
Time frame: 24 months
Crohn's Disease Endoscopic Index of Severity (CDEIS)
Time frame: 24 months
Rutgeerts endoscopic score
Time frame: 24 months
Harvey & Bradshaw Index (HBI)
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2021.
- Individual participant dataSharing planned: Yes. The main objective is to observe the safety and clinical benefit of autologous HSCT therapy in refractory patients with Crohn's disease. Evaluation during transplant period and 1, 3, 6, 12 and 24 months post-transplant. Safety be evaluated by the amount of treatment-related adverse events. Record adverse events in a standardized way. Secondary outcome measures will be disease remission: 1, 3, 6, 12 and 24 months post-transplant both clinical and endoscopic remission. The percentage of patients in sustained disease remission at 1, 3, 6, 12 and 24 months post HSCT will be determined. Sustained disease remission is defined as a CDAI < 150; HBI <4, CCSI< 16, without the use of corticosteroids, immunosuppressant or biologic agents. Mucosal healing will be assessed during ileocolonoscopy at 6, 12, and 24 months following HSCT using SES, CDEIS and Rutgeerts endoscopy index. Heath Quality life, Short Form 36 and IBDQ at 1 3 6 12 and 24 months post-Transplant.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Milton A Ruiz, MD, PhD principal investigator
Beneficencia Portuguesa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Autologous Hematopoietic Stem Cell Transplantation in people with Crohn's Disease and Inflammatory Bowel Diseases, run by Beneficência Portuguesa de São Paulo at 1 site in Brazil.
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 13 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 15 Jan 2021. 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 Brazil. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of unselected autologous HSCT in refractory Crohn´s disease patients (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jan 2021; AzTrials last refreshed its copy on 7 Nov 2026.