Autologous Transplant Targeted Against Crohn's

Crohn's Disease Clinical Trial

— ATTAC  

Official title:

Autologous Hematopoietic Stem Cell Transplant for Crohn's Disease

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04154735
• Other study ID #: DIAD.ATTAC.2018
• Status: Withdrawn
• Phase: Phase 2
• Start date: November 2019
• Est. completion date: March 2024

Study information

• Verified date: January 2019
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a new Phase II trial to assess the toxicity and efficacy of autologous hematopoietic stem cell transplantation (HSCT) utilizing a new non-myeloablative conditioning regimen in patients with high-risk Crohn's disease (CD). The regimen will include low-dose immunosuppressive therapy and a targeted antibiotic for six to twelve months post-HSCT.

Description:

The autologous hematopoietic stem cell transplantation (HSCT) in this study utilizes a new non-myeloablative conditioning regimen in patients with high-risk Crohn's disease (CD). The regimen includes two types of chemotherapy (cyclophosphamide and fludarabine) as well as alemtuzumab. The regimen will include low-dose immunosuppressive therapy with tacrolimus (Prograf) for one year post-HSCT in attempt to prevent relapse and improve long-term remission. Patients will also receive rifaximin (Xifaxan) for six months post-HSCT to target abnormal intestinal microbiota that may trigger intestinal inflammation. The ability of these experimental treatments to stop relapses and progression (worsening) of Crohn's disease will be assessed.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2024
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

1. Age 18 years and less than age 50 years at the time of pre-transplant evaluation

2. Ability to give informed consent

3. An established clinical diagnosis of severe Crohn's Disease* that has failed therapy with prednisone or budesonide (Entocort) and either a or b below:

1. At least two anti-tumor necrosis factor (TNF) drugs (e.g., infliximab (Remicade), adalimumab (Humira), or certolizumab pegol (Cimzia))

2. One anti-TNF drug as above and either vedolizumab (Entyvio) or ustekinumab (Stelara)

• Severe Crohn's Disease is defined as a CDAI (see Appendix A) of 250 to 400 or a Craig's Crohn's Severity Index (CCSI, see Appendix B) that is > 17.

Exclusion Criteria:

1. Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment

2. Prior history of malignancy (except localized basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix). Other malignancies for which the patient is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis

3. Positive pregnancy test, inability to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy

4. HIV positive

5. Hepatitis B or C positive

6. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible

7. Untreated life-threatening cardiac arrhythmia on EKG or 24-hour holter or history of coronary artery disease or congestive heart failure

8. Left ventricular ejection fraction (LVEF) <50%

9. Forced vital capacity (FVC) <60% of predicted after bronchodilator therapy (if necessary) or diffusing capacity of the lungs for carbon monoxide (DLCO) hemoglobin corrected <60 % predicted

10. Serum creatinine >2 mg/dl

11. 24-hour urine creatinine clearance <90

12. Liver transaminases >2x of normal limits, or bilirubin >2 mg/dl unless due to Crohn's Disease

13. Major hematological abnormalities such as platelet count < 100,000/ul or absolute neutrophil count (ANC) < 1500/ul

14. Failure to collect at least 2 x10^6 cluster of differentiation 34 (CD34+) cells/kg

15. Any active infection

16. Known hypersensitivity to mouse, rabbit, or E. coli derived proteins

17. Short Bowel Syndrome defined as intestinal dysfunction with the presence of significant malabsorption of both macronutrients and micronutrients or when gastrointestinal function is inadequate to maintain nutrient and hydration status without intravenous or enteral supplementation.

18. History of anorexia nervosa (serum albumin = 20 g/L, body mass index = 18)

19. Patients presenting with intestinal perforation or toxic megacolon or a problem that will require urgent surgery. The presence of intestinal stomas, strictures, or fistulae does not exclude the patient from study.

20. Unable or unwilling to stop using and/or smoking tobacco products

21. Abnormal peripheral blood cytogenetics

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Fludarabine
A chemotherapy medication commonly used in the treatment of leukemia and lymphoma
• Cyclophosphamide
A medication used as chemotherapy and to suppress the immune system
• Mesna
A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder
• Alemtuzumab
A protein that kills the immune cells that are thought to be causing Crohn's; it is commonly used in the treatment of leukemia and lymphoma
• G-CSF
A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
• Rifaximin
An antibiotic used to treat irritable bowel syndrome and relapsing C. difficile infection; it inhibits DNA-dependent RNA polymerase
• Tacrolimus
A medication which suppresses the immune system and inhibits T-lymphocytes; commonly used to lower the risk of organ rejection following transplant

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related mortality	Treatment-related mortality	3 years
Primary	Overall survival	Survival of participants	3 years
Primary	Clinical remission	Change of Crohn's Disease Activity Index CDAI = 150, Harvey-Bradshaw Index (HBI) =4, may be on immune suppressive drugs	6 months, 1 year, 2 years, 3 years
Primary	Complete remission	Change of Clinical, endoscopic, and histologic remission on no immune modulating drugs	1 year, 2 years, 3 years
Secondary	Craig's Crohn's Severity Index	Improvement in the severity of Crohn's Disease according to the Craig's Crohn's Severity Index (CDAI)	6 months, 1 year, 2 years, 3 years
Secondary	Endoscopic severity scales	Improvement on the Simple Endoscopic Score for Crohn's Disease (SES-CD)	6 months, 1 year, 2 years, 3 years
Secondary	Histologic remission on colonoscopy with biopsy	No evidence of disease on biopsy	6 months, 1 year, 2 years, 3 years
Secondary	Endoscopic remission	No evidence of disease on colonoscopy	6 months, 1 year, 2 years, 3 years
Secondary	Drug-free clinical remission	Crohn's Disease Activity Index (CDAI = 150),Harvey Bradshaw Index HBI =4, no immune suppressive drugs	1 year, 2 years, 3 years
Secondary	Relapse-free survival	Relapse is defined as Crohn's Disease Activity Index CDAI >150, Harvey Bradshaw Index HBI >4, and restarting or increasing immune based medication(s)	6 months, 1 year, 2 years, 3 years
Secondary	Stool markers	Improvement in fecal calprotectin and fecal lactoferrin	6 months, 1 year, 2 years, 3 years
Secondary	Quality of life short form Survey (SF-36)	Improvement in quality of life, measured by 36-Item Short Form Survey (SF-36) The evaluation of the results was done by attributing scores to each question, which were then transformed into a scale ranging from 0 to 100, where 0 corresponds to the worst quality of life and 100 to the best.	6 months, 1 year, 2 years, 3 years
Secondary	Inflammatory Bowel Disease Questionnaire	Improvement on the Inflammatory Bowel Disease Questionnaire (IBDQ) Total IBDQ score ranges from 32 to 224. A higher score indicates better quality of life.	6 months, 1 year, 2 years, 3 years
Secondary	Crohn's Disease Endoscopic Index of Severity (CDEIS)	Improvement on the Crohn's Disease Endoscopic Index of Severity (CDEIS)	6 months, 1 year, 2 years, 3 years