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Crohn's DiseasePhase 2ATTACNCT04154735

Autologous Transplant Targeted Against Crohn's

A Phase 2 study testing Fludarabine, Cyclophosphamide and Mesna in people with Crohn's Disease, run by Northwestern University at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 49 years
Conditions the study is for
Crohn's Disease
What is being tested?
Fludarabine, Cyclophosphamide and Mesna
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Nov 2019to Mar 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 49 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 21Show fewer
  • 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
  • 24-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
  • Known hypersensitivity to mouse, rabbit, or E. coli derived proteins
  • 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.
  • History of anorexia nervosa (serum albumin ≤ 20 g/L, body mass index ≤ 18)
  • 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.
  • Unable or unwilling to stop using and/or smoking tobacco products
  • Abnormal peripheral blood cytogenetics

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: Autologous Hematopoietic Stem Cell Transplant for Crohn's Disease

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.

Read the 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
Being tested
Fludarabine, Cyclophosphamide, Mesna, Alemtuzumab, G-CSF
Keywords
Autologous Stem Cell Transplantation, Hematopoietic Stem Cell Transplant
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

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

  • CyclophosphamideDrug

    Also called Cytoxan

    A medication used as chemotherapy and to suppress the immune system

  • MesnaDrug

    Also called Mesnex

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

  • AlemtuzumabDrug

    Also called Lemtrada, Campath

    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-CSFDrug

    Also called Neupogen, Filgrastim, Granix, Zarxio

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

  • RifaximinDrug

    Also called Xifaxan

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

  • TacrolimusDrug

    Also called Prograf, Envarsus XR, Stargraf XL

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

Study groups in NCT04154735
Study groupRoleWhat they receive
Hematopoietic Stem Cell TransplantationExperimentalHematopoietic 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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Mesna; Drug: Alemtuzumab; Drug: G-CSF; Drug: Rifaximin; Drug: Tacrolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment-related mortality

    Treatment-related mortality

    Measured: 3 years

  2. Overall survival

    Survival of participants

    Measured: 3 years

  3. Clinical remission

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

    Measured: 6 months, 1 year, 2 years, 3 years

  4. Complete remission

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

    Measured: 1 year, 2 years, 3 years

Secondary outcomes (10)

  1. Craig's Crohn's Severity Index

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

    Measured: 6 months, 1 year, 2 years, 3 years

  2. Endoscopic severity scales

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

    Measured: 6 months, 1 year, 2 years, 3 years

  3. Histologic remission on colonoscopy with biopsy

    No evidence of disease on biopsy

    Measured: 6 months, 1 year, 2 years, 3 years

  4. Endoscopic remission

    No evidence of disease on colonoscopy

    Measured: 6 months, 1 year, 2 years, 3 years

  5. Drug-free clinical remission

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

    Measured: 1 year, 2 years, 3 years

  6. Relapse-free survival

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

    Measured: 6 months, 1 year, 2 years, 3 years

  7. Stool markers

    Improvement in fecal calprotectin and fecal lactoferrin

    Measured: 6 months, 1 year, 2 years, 3 years

  8. Quality of life short form Survey (SF-36)

    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.

    Measured: 6 months, 1 year, 2 years, 3 years

  9. Inflammatory Bowel Disease Questionnaire

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

    Measured: 6 months, 1 year, 2 years, 3 years

  10. Crohn's Disease Endoscopic Index of Severity (CDEIS)

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

    Measured: 6 months, 1 year, 2 years, 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2019
  2. Study startNov 2019 (estimated)
  3. Primary completionMar 2023 (estimated)
  4. Study completionMar 2024 (estimated)

Why it stopped: Discontinued by Investigator

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04154735
Sponsor's protocol ID
DIAD.ATTAC.2018
Acronym
ATTAC
Status last verified
Jan 2019
First submitted
8 Mar 2019
Last updated
8 Nov 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine, Cyclophosphamide and Mesna in people with Crohn's Disease, run by Northwestern University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 8 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment-related mortality (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04154735.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2019.

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