Clinical trial NCT04154735: Autologous Transplant Targeted Against Crohn's
Official title: Autologous Hematopoietic Stem Cell Transplant for Crohn's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Autologous Stem Cell Transplantation
Hematopoietic Stem Cell Transplant
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2019-11-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-related mortality
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
measure: Clinical remission
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Complete remission
timeFrame: 1 year, 2 years, 3 years
Secondary outcomes:
measure: Craig's Crohn's Severity Index
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Endoscopic severity scales
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Histologic remission on colonoscopy with biopsy
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Endoscopic remission
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Drug-free clinical remission
timeFrame: 1 year, 2 years, 3 years
measure: Relapse-free survival
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Stool markers
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Quality of life short form Survey (SF-36)
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Inflammatory Bowel Disease Questionnaire
timeFrame: 6 months, 1 year, 2 years, 3 years
measure: Crohn's Disease Endoscopic Index of Severity (CDEIS)
timeFrame: 6 months, 1 year, 2 years, 3 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Richard Burt, MD
role: PRINCIPAL_INVESTIGATOR
References: