Autologous Transplant Targeted Against Crohn's

NCT04154735 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: DIAD.ATTAC.2018
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Crohn's Disease

Keywords

Autologous Stem Cell Transplantation; Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (4)

• Treatment-related mortality

  Treatment-related mortality

  3 years

• Overall survival

  Survival of participants

  3 years

• 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

• Complete remission

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

  1 year, 2 years, 3 years

Secondary Outcomes (10)

• Craig's Crohn's Severity Index

  6 months, 1 year, 2 years, 3 years

• Endoscopic severity scales

  6 months, 1 year, 2 years, 3 years

• Histologic remission on colonoscopy with biopsy

  6 months, 1 year, 2 years, 3 years

• Endoscopic remission

  6 months, 1 year, 2 years, 3 years

• Drug-free clinical remission

  1 year, 2 years, 3 years

Study Arms (1)

Hematopoietic Stem Cell Transplantation

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Mesna; Drug: Alemtuzumab; Drug: G-CSF; Drug: Rifaximin; Drug: Tacrolimus

Interventions

Fludarabine DRUG

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

Hematopoietic Stem Cell Transplantation

Cyclophosphamide DRUG

A medication used as chemotherapy and to suppress the immune system

Also known as: Cytoxan

Hematopoietic Stem Cell Transplantation

Mesna DRUG

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

Also known as: Mesnex

Hematopoietic Stem Cell Transplantation

Alemtuzumab 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

Also known as: Lemtrada, Campath

Hematopoietic Stem Cell Transplantation

G-CSF DRUG

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

Also known as: Neupogen, Filgrastim, Granix, Zarxio

Hematopoietic Stem Cell Transplantation

Rifaximin DRUG

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

Also known as: Xifaxan

Hematopoietic Stem Cell Transplantation

Tacrolimus DRUG

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

Also known as: Prograf, Envarsus XR, Stargraf XL

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 years and less than age 50 years at the time of pre-transplant evaluation
• Ability to give informed consent
• An established clinical diagnosis of severe Crohn's Disease\* that has failed therapy with prednisone or budesonide (Entocort) and either a or b below:
• At least two anti-tumor necrosis factor (TNF) drugs (e.g., infliximab (Remicade), adalimumab (Humira), or certolizumab pegol (Cimzia))
• 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.

You may not qualify if:

• 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
• 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
• 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
• HIV positive
• Hepatitis B or C positive
• Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
• Untreated life-threatening cardiac arrhythmia on EKG or 24-hour holter or history of coronary artery disease or congestive heart failure
• Left ventricular ejection fraction (LVEF) \<50%
• 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
• Serum creatinine \>2 mg/dl
• hour urine creatinine clearance \<90
• Liver transaminases \>2x of normal limits, or bilirubin \>2 mg/dl unless due to Crohn's Disease
• Major hematological abnormalities such as platelet count \< 100,000/ul or absolute neutrophil count (ANC) \< 1500/ul
• Failure to collect at least 2 x10\^6 cluster of differentiation 34 (CD34+) cells/kg
• Any active infection

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

fludarabine; Cyclophosphamide; Mesna; Alemtuzumab; Granulocyte Colony-Stimulating Factor; Filgrastim; Rifaximin; Tacrolimus

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Macrolides; Lactones

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Chief, Immunotherapy and Autoimmune Diseases

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: November 6, 2019
• Study Start: November 1, 2019
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2024
• Last Updated: November 8, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)