High dose immunoablation followed by stem cell transplantation for Crohn's disease

Autologous Hematopoietic Stem Cell Transplantation for Refractory Crohn's Disease

This study is testing whether a high dose of immune treatment followed by a stem cell transplant can help people with severe Crohn's disease who haven't found relief from regular treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 13 Years to 28 Years
• Sex: All
• Sponsor: Cedars-Sinai Medical Center (other)
• Drugs / interventions: infliximab, adalimumab, certolizumab, methotrexate
• Locations: 1 site (Los Angeles, California)
• Trial ID: NCT04224558 on ClinicalTrials.gov

What this trial studies

This study investigates the use of high dose immunoablation followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn's disease who have not responded to conventional therapies. The approach involves removing overactive lymphocytes to reset the immune system, potentially leading to long-term disease control. The study is open-label and non-randomized, focusing on evaluating the safety and clinical benefits of this treatment in a specific patient population. Participants will be monitored for transplant-related mortality and severe toxicity within the first six months post-transplant.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 13-28 with active Crohn's disease who have not achieved satisfactory results from multiple immunosuppressive therapies.

Not a fit: Patients who are not experiencing severe Crohn's disease or those who have not failed conventional treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for long-term disease control in patients with refractory Crohn's disease.

How similar studies have performed: While the approach is novel for Crohn's disease, similar strategies using HSCT have shown promise in other autoimmune conditions.

Eligibility criteria

Inclusion Criteria:

1. Aged 13-28 years are eligible
2. Confirmed diagnosis of active Crohn's disease:

   1. Diagnosis of Crohn's disease based on typical radiological appearances and / or typical histology at least 6 months prior to screening.
   2. Active disease at the time of registration to the trial, defined as

   i) PCDAI \> 30, and ii) Two of the following:
   1. elevated CRP
   2. endoscopic evidence of active disease confirmed by histology
   3. clear evidence of active small bowel Crohn's disease on CT or MR enterography.
3. Unsatisfactory course despite 3 immunosuppressive agents (usually azathioprine, methotrexate and infliximab, adalimumab and/or certolizumab) in addition to corticosteroids. Patients should have relapsing disease (i.e. 1 exacerbation/year) despite thiopurines, methotrexate and/or infliximab/adalimumab/certolizumab maintenance therapy or clear demonstration of intolerance / toxicity to these drugs.
4. Current problems unsuitable for surgery or patient at risk for developing short bowel syndrome.
5. Accepted by a majority of the members of the combined IBD Center as an appropriate candidate (see Selection description below).
6. Informed consent

   1. Prepared to undergo additional study procedures as per trial schedule
   2. Patient has undergone intensive counseling about risks

Exclusion Criteria:

1. Pregnancy or unwillingness to use adequate contraception during the study, in women of childbearing age. Unwillingness of using appropriate contraceptive measures in males.
2. Concomitant severe disease

   1. renal: creatinine clearance \< 30 mL/min (measured or estimated)
   2. cardiac: clinical evidence of refractory congestive heart failure; left ventricular ejection fraction \< 40% by cardiac echo; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with hemodynamic consequences as evaluated by an experienced echo cardiographer
   3. pulmonary: diffusion capacity \<40%
   4. psychiatric disorders including active drug or alcohol abuse
   5. concurrent or recent history of malignant disease (excluding non-melanoma skin cancer)
   6. uncontrolled hypertension, defined as resting systolic blood pressure ≥ 140 and/or resting diastolic pressure ≥ 90 despite at least 2 anti-hypertensive agents.
   7. any infection with HIV, HTLV-1 or 2, hepatitis viruses, or any other infection the investigators consider a contraindication to participation.
   8. other chronic disease causing significant organ failure.
3. Infection or risk thereof:

   1. Current clinical relevant abscess or significant active infection.
   2. Perianal fistula without free drainage. Perianal fistulas is not an exclusion provided there is natural free drainage or a seton suture(s) have been placed.
   3. History of tuberculosis or at current increased risk of tuberculosis
   4. Quantiferon Gold test result or other investigations that the investigators regard as evidence of active tuberculosis.
   5. Abnormal chest X-ray (CXR) consistent with active infection or neoplasm.

6\) Significant malnutrition: Body Mass Index (BMI) ≤ 18, serum albumin \< 20 g/l.

7\) Previous poor compliance. 8) Concurrent enrollment in any other protocol using an investigational drug or hematopoietic growth factor up to four weeks before study entry.

Where this trial is running

Los Angeles, California

• Cedars-Sinai Medical Center — Los Angeles, California, United States (RECRUITING)

Study contacts

• Principal investigator: David Ziring, MD — Cedars-Sinai Medical Center
• Study coordinator: David Ziring, MD

Conditions: Crohn Disease