Autologous Unselected Hematopoietic Stem Cell Transplantation for Refractory Crohn's Disease

NCT03000296 | Unknown DMC

• 1 other identifier: autocrohnproject1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 disease. Adverse events, and clinical and endoscopic conditions will be assessed at different short and long-term time points.

Conditions

Crohn's Disease; Inflammatory Bowel Diseases; Gastroenteritis

Keywords

autologous; lymphoablation; hematopoetic stem cell transplant; immune system; Bone marrow transplant

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (8)

• Crohn´s Disease Activity Index (CDAI)

  12 months

• CRAIG Crohn´s Severity Score (CSS)

  12 months

• Inflammatory Bowel Disease Questionnaire (IBDQ)

  24 months

• Short Form-36 Health Survey (SF-36)

  24 months

• Simple Endoscopic Activity Score (SES)

  24 months

Study Arms (1)

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.

Procedure: Autologous Hematopoietic Stem Cell Transplantation

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Hematopoietic stem cell transplantation Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system.

Also known as: Bone Marrow Transplantation, Hematopoietic Stem Cell Transplatation

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

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 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
• 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.

Sponsors & Collaborators

• Beneficência Portuguesa de São Paulo: lead

Study Sites (1)

Beneficencia Portuguesa

São José do Rio Preto, São Paulo, 15015-750, Brazil

Location

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis

Interventions

Bone Marrow Transplantation

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Milton A Ruiz, MD, PhD

  Beneficencia Portuguesa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PhD.

Study Record Dates

• First Submitted: December 9, 2016
• First Posted: December 22, 2016
• Study Start: October 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2024
• Last Updated: January 15, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share

Locations

BR (1)