Autologous Transplant Targeted Against Crohn's

NCT ID: NCT04154735

Last Updated: 2019-11-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-30
• Study Completion Date: 2024-03-31

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.

Conditions

Crohn's Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

A chemotherapy medication commonly used in the treatment of leukemia and lymphoma

Cyclophosphamide

Intervention Type: DRUG

A medication used as chemotherapy and to suppress the immune system

Mesna

Intervention Type: DRUG

A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder

Alemtuzumab

Intervention Type: DRUG

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

Intervention Type: DRUG

A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

Rifaximin

Intervention Type: DRUG

An antibiotic used to treat irritable bowel syndrome and relapsing C. difficile infection; it inhibits DNA-dependent RNA polymerase

Tacrolimus

Intervention Type: DRUG

A medication which suppresses the immune system and inhibits T-lymphocytes; commonly used to lower the risk of organ rejection following transplant

Interventions

Fludarabine

A chemotherapy medication commonly used in the treatment of leukemia and lymphoma

Intervention Type: DRUG

Cyclophosphamide

A medication used as chemotherapy and to suppress the immune system

Intervention Type: DRUG

Mesna

A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder

Intervention Type: 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

Intervention Type: DRUG

G-CSF

A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

Intervention Type: DRUG

Rifaximin

An antibiotic used to treat irritable bowel syndrome and relapsing C. difficile infection; it inhibits DNA-dependent RNA polymerase

Intervention Type: DRUG

Tacrolimus

A medication which suppresses the immune system and inhibits T-lymphocytes; commonly used to lower the risk of organ rejection following transplant

Intervention Type: DRUG

Other Intervention Names

Cytoxan; Mesnex; Lemtrada; Campath; Neupogen; Filgrastim; Granix; Zarxio; Xifaxan; Prograf; Envarsus XR; Stargraf XL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Richard Burt, MD

Division Chief, Immunotherapy and Autoimmune Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard Burt, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

DIAD.ATTAC.2018

Identifier Type: -

Identifier Source: org_study_id