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Autologous Transplant Targeted Against Crohn's (ATTAC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04154735
Recruitment Status : Withdrawn (Discontinued by Investigator)
First Posted : November 6, 2019
Last Update Posted : November 8, 2019
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, 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.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Fludarabine Drug: Cyclophosphamide Drug: Mesna Drug: Alemtuzumab Drug: G-CSF Drug: Rifaximin Drug: Tacrolimus Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Autologous Hematopoietic Stem Cell Transplant for Crohn's Disease
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: Hematopoietic Stem Cell Transplantation
Hematopoietic 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.
Drug: Fludarabine
A chemotherapy medication commonly used in the treatment of leukemia and lymphoma

Drug: Cyclophosphamide
A medication used as chemotherapy and to suppress the immune system
Other Name: Cytoxan

Drug: Mesna
A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder
Other Name: Mesnex

Drug: 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
Other Names:
  • Lemtrada
  • Campath

Drug: G-CSF
A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
Other Names:
  • Neupogen
  • Filgrastim
  • Granix
  • Zarxio

Drug: Rifaximin
An antibiotic used to treat irritable bowel syndrome and relapsing C. difficile infection; it inhibits DNA-dependent RNA polymerase
Other Name: Xifaxan

Drug: Tacrolimus
A medication which suppresses the immune system and inhibits T-lymphocytes; commonly used to lower the risk of organ rejection following transplant
Other Names:
  • Prograf
  • Envarsus XR
  • Stargraf XL




Primary Outcome Measures :
  1. Treatment-related mortality [ Time Frame: 3 years ]
    Treatment-related mortality

  2. Overall survival [ Time Frame: 3 years ]
    Survival of participants

  3. Clinical remission [ Time Frame: 6 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

  4. Complete remission [ Time Frame: 1 year, 2 years, 3 years ]
    Change of Clinical, endoscopic, and histologic remission on no immune modulating drugs


Secondary Outcome Measures :
  1. Craig's Crohn's Severity Index [ Time Frame: 6 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)

  2. Endoscopic severity scales [ Time Frame: 6 months, 1 year, 2 years, 3 years ]
    Improvement on the Simple Endoscopic Score for Crohn's Disease (SES-CD)

  3. Histologic remission on colonoscopy with biopsy [ Time Frame: 6 months, 1 year, 2 years, 3 years ]
    No evidence of disease on biopsy

  4. Endoscopic remission [ Time Frame: 6 months, 1 year, 2 years, 3 years ]
    No evidence of disease on colonoscopy

  5. Drug-free clinical remission [ Time Frame: 1 year, 2 years, 3 years ]
    Crohn's Disease Activity Index (CDAI ≤ 150),Harvey Bradshaw Index HBI ≤4, no immune suppressive drugs

  6. Relapse-free survival [ Time Frame: 6 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)

  7. Stool markers [ Time Frame: 6 months, 1 year, 2 years, 3 years ]
    Improvement in fecal calprotectin and fecal lactoferrin

  8. Quality of life short form Survey (SF-36) [ Time Frame: 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.

  9. Inflammatory Bowel Disease Questionnaire [ Time Frame: 6 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.

  10. Crohn's Disease Endoscopic Index of Severity (CDEIS) [ Time Frame: 6 months, 1 year, 2 years, 3 years ]
    Improvement on the Crohn's Disease Endoscopic Index of Severity (CDEIS)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04154735


Locations
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United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
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Principal Investigator: Richard Burt, MD Northwestern University
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Responsible Party: Richard Burt, MD, Division Chief, Immunotherapy and Autoimmune Diseases, Northwestern University
ClinicalTrials.gov Identifier: NCT04154735    
Other Study ID Numbers: DIAD.ATTAC.2018
First Posted: November 6, 2019    Key Record Dates
Last Update Posted: November 8, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Richard Burt, MD, Northwestern University:
Autologous Stem Cell Transplantation
Hematopoietic Stem Cell Transplant
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Rifaximin
Cyclophosphamide
Fludarabine
Alemtuzumab
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Immunological
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents