Autologous Transplant Targeted Against Crohn's

Registration Number
NCT04154735
Lead Sponsor
Northwestern University
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...

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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.
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Hematopoietic Stem Cell TransplantationFludarabineHematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
Hematopoietic Stem Cell TransplantationCyclophosphamideHematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
Hematopoietic Stem Cell TransplantationMesnaHematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
Hematopoietic Stem Cell TransplantationAlemtuzumabHematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
Hematopoietic Stem Cell TransplantationG-CSFHematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
Hematopoietic Stem Cell TransplantationRifaximinHematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
Hematopoietic Stem Cell TransplantationTacrolimusHematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
Primary Outcome Measures
NameTimeMethod
Treatment-related mortality3 years

Treatment-related mortality

Overall survival3 years

Survival of participants

Clinical remission6 months, 1 year, 2 years, 3 years

Change of Crohn's Disease Activity Index CDAI ≤ 150, Harvey-Bradshaw Index (HBI) ≤4, may be on immune suppressive drugs

Complete remission1 year, 2 years, 3 years

Change of Clinical, endoscopic, and histologic remission on no immune modulating drugs

Secondary Outcome Measures
NameTimeMethod
Histologic remission on colonoscopy with biopsy6 months, 1 year, 2 years, 3 years

No evidence of disease on biopsy

Endoscopic remission6 months, 1 year, 2 years, 3 years

No evidence of disease on colonoscopy

Craig's Crohn's Severity Index6 months, 1 year, 2 years, 3 years

Improvement in the severity of Crohn's Disease according to the Craig's Crohn's Severity Index (CDAI)

Endoscopic severity scales6 months, 1 year, 2 years, 3 years

Improvement on the Simple Endoscopic Score for Crohn's Disease (SES-CD)

Drug-free clinical remission1 year, 2 years, 3 years

Crohn's Disease Activity Index (CDAI ≤ 150),Harvey Bradshaw Index HBI ≤4, no immune suppressive drugs

Inflammatory Bowel Disease Questionnaire6 months, 1 year, 2 years, 3 years

Improvement on the Inflammatory Bowel Disease Questionnaire (IBDQ) Total IBDQ score ranges from 32 to 224. A higher score indicates better quality of life.

Crohn's Disease Endoscopic Index of Severity (CDEIS)6 months, 1 year, 2 years, 3 years

Improvement on the Crohn's Disease Endoscopic Index of Severity (CDEIS)

Relapse-free survival6 months, 1 year, 2 years, 3 years

Relapse is defined as Crohn's Disease Activity Index CDAI \>150, Harvey Bradshaw Index HBI \>4, and restarting or increasing immune based medication(s)

Stool markers6 months, 1 year, 2 years, 3 years

Improvement in fecal calprotectin and fecal lactoferrin

Quality of life short form Survey (SF-36)6 months, 1 year, 2 years, 3 years

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.

Trial Locations

Locations (1)

Northwestern University

🇺🇸

Chicago, Illinois, United States

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