Crohn's Disease
Stem Cell Transplant After High-Dose Therapy for Severe Crohn’s Disease
This phase 1/2 study is evaluating the safety and effectiveness of high-dose chemotherapy followed by an infusion of a participant’s own CD34-selected blood stem cells in children and adults with severe Crohn’s disease.
Registry title: Autologous Stem Cell Transplantation for Crohn's Disease
2 recruiting U.S. sites ↓Study at a glance
- Age
- 10 Years–60 Years
- Treatment
- autologous CD34-selected peripheral blood stem cells transplant or Alemtuzumab
- Design
- Not provided
- Central study contact
- Shawna H McIntyre, RN412-692-5552 ext. 4126925552mcintyresm@upmc.edu
- Sponsor
- Paul Szabolcs
Research question
What regimen-related toxicities, life-threatening infections, and changes in Crohn’s disease activity occur when people with severe Crohn’s disease receive high-dose chemotherapy followed by their own CD34-selected peripheral blood stem cells?
Participant snapshot
Who the study is looking for
- The study is looking for people ages 10 through 60 with Crohn’s disease.
- The study is looking for people with active or severe disease based on specified Crohn’s disease activity scores.
- Examples include people with severe recurrent, widespread, treatment-resistant, steroid-dependent, or medically unresponsive Crohn’s disease or complications.
- Participants must have no surgical treatment option because of short-bowel-syndrome risk or because they refuse surgery; people with stomas may be considered.
Participation overview
What participation may involve
Participants undergo stem-cell mobilization, transplant conditioning with several drugs, and infusion of their own CD34-selected peripheral blood stem cells, followed by assessments of toxicity, infection, Crohn’s disease activity, blood-cell recovery, immune recovery, and longer-term complications. What participation may involve: - Receive cyclophosphamide, G-CSF, and mesna as the registry-listed stem-cell mobilization regimen. - Receive transplant conditioning that may include alemtuzumab, ATG, melphalan, thiotepa, and rituximab. - Receive an infusion of autologous, meaning the participant’s own, CD34-selected peripheral blood stem cells. - Undergo follow-up assessments for regimen-related toxicities, life-threatening infections, Crohn’s disease activity, blood-cell recovery, immune recovery, cardiac and endocrine complications, and biomarkers.
Study interventions
What participants may receive or do
- autologous CD34-selected peripheral blood stem cells transplant: Participants receive high-dose immune therapy followed by an infusion of CD34-selected peripheral blood stem cells collected from their own body.
- Alemtuzumab: The registry lists alemtuzumab, also called Campath-1H, as part of transplant conditioning.
- ATG: The registry lists rabbit anti-thymocyte globulin (ATG), also called Thymoglobulin, as part of transplant conditioning.
- Melphalan: The registry lists melphalan as part of transplant conditioning.
- Thiotepa: The registry lists thiotepa as part of transplant conditioning.
- Rituximab: The registry lists rituximab, also called Rituxan, as part of transplant conditioning.
- Cyclophosphamide: The registry lists cyclophosphamide, also called Cytoxan, as part of stem-cell mobilization.
- G-CSF: The registry lists granulocyte colony-stimulating factor (G-CSF), including filgrastim names, as part of stem-cell mobilization.
- Mesna: The registry lists mesna as part of stem-cell mobilization.
Study design
How the comparison works
This is an open-label phase 1/2 treatment study in which an estimated 20 participants are assigned to one experimental group receiving the transplant regimen. The registry reports allocation as not applicable and uses a single-group design, so participants are not randomized among multiple study groups. The study is open-label, meaning the registry reports no masking. The registry describes only one experimental group and does not report a separate comparison group. No placebo intervention or placebo group is described in the registry record.
Reported activities
Procedures and tests
- Stem-cell mobilization using the registry-listed drugs cyclophosphamide, G-CSF, and mesna.
- High-dose transplant conditioning followed by infusion of autologous CD34-selected peripheral blood stem cells.
- Crohn’s disease activity assessments using the Harvey-Bradshaw Index, Crohn’s Disease Activity Index, or Pediatric Crohn’s Disease Activity Index.
- Monitoring for regimen-related toxicities and life-threatening infections.
- Blood tests or assessments tracking absolute neutrophil count and platelet recovery.
- Assessment of T-cell recovery, immune dysregulation, and biomarkers associated with relapse.
- Monitoring for long-term cardiac and endocrine complications.
- Screening must confirm specified platelet, neutrophil, creatinine, and bilirubin levels.
- Screening must confirm heart function using resting left ventricular ejection fraction or shortening fraction and review any history of coronary artery disease.
- Screening must confirm lung function using FEV1/FVC and diffusing capacity of the lungs for carbon monoxide.
- Pregnancy testing is required for females age 10 or older or who have reached menarche unless surgically sterilized.
- Screening includes viral-status requirements for HIV, HTLV, hepatitis B surface antigen, and hepatitis C RNA.
- Appropriate confirmatory testing, such as blood cultures or polymerase chain reaction testing, may be used to check for active infection before mobilization and high-dose chemotherapy.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be 10 through 60 years old when informed consent is provided.
- The participant or guardian must be able to understand and provide informed consent.
- Disease activity must exceed at least one stated threshold: Harvey-Bradshaw Index or Crohn’s disease activity score above 5, CDAI above 250, or PCDAI above 30.
- There must be no surgical treatment option because of short-bowel-syndrome risk or because the patient refuses surgery.
- The platelet count must be greater than 100,000 per cubic millimeter.
- The absolute neutrophil count must be greater than 1,500 per cubic millimeter unless the low count is caused by 6-MP therapy.
- Heart testing must show a resting left ventricular ejection fraction of at least 40% or a shortening fraction of at least 26%, with no history of coronary artery disease.
- Lung testing must show FEV1/FVC and diffusing capacity values at least 60% of the predicted value for age.
- People who could become pregnant need a negative pregnancy test as specified by the protocol.
- People with reproductive potential must agree to use an FDA-approved birth-control method for up to 24 months after transplant or while taking medication that may harm a pregnancy.
Possible reasons someone may not be able to join
- People are excluded if they have not received adequate dosing of 6-MP, 5-ASA products, and metronidazole.
- People are excluded if they had a sustained response without corticosteroids after four months of anti-TNF, anti-integrin, or anti-IL-12/23 therapy.
- Toxic megacolon or intestinal perforation excludes participation.
- A conjugated bilirubin level above 2.0 mg/dL excludes participation.
- Pregnant or nursing people are excluded.
- Positive results for HIV or HTLV antibodies, hepatitis B surface antigen, or hepatitis C RNA by PCR exclude participation.
- An active infection confirmed within two weeks of mobilization and high-dose chemotherapy excludes participation.
- The investigator may exclude someone for other medical findings that add risk, interfere with study requirements, or affect interpretation of the data.
Important unknowns
What the record does not make clear
- The registry does not state how many visits, hospital stays, or follow-up appointments participation requires.
- Several outcomes are assessed through 24 months after transplant, but the registry does not state the total participation duration.
- The registry does not explain which Crohn’s medicines may continue during mobilization, conditioning, transplant, or follow-up.
- The registry does not provide washout periods for corticosteroids, biologics, immunomodulators, antibiotics, or other Crohn’s treatments.
- The registry does not describe rescue treatment if Crohn’s disease worsens or serious complications occur.
- The registry does not state whether colonoscopy, upper endoscopy, capsule endoscopy, or biopsy is required.
- The registry does not identify which treatment, testing, hospitalization, or follow-up costs are paid by the study or billed to insurance.
- The registry does not report whether participants receive compensation.
- The registry does not report travel, lodging, parking, meal, or caregiver support for participation in Pittsburgh.
- The registry does not state whether any screening or follow-up can occur remotely or through a local clinician.
- The registry does not describe post-study medical follow-up or access to study-related care after formal participation ends.
Before contacting the site
Questions for the study team
- What are the expected hospital stays, outpatient visits, and follow-up schedule from screening through the end of participation?
- Which conditioning drugs listed in the registry would I actually receive, and what determines the exact regimen?
- Which Crohn’s medicines must be continued, tapered, or stopped before mobilization, conditioning, and transplant?
- What immediate and long-term transplant risks should participants expect, and how are serious infections or other complications prevented and managed?
- Are colonoscopies, imaging studies, biopsies, or other gastrointestinal procedures required during screening or follow-up?
- Which study-related treatments, tests, hospitalizations, travel, and lodging are covered, and could anything be billed to insurance?
- Can screening or follow-up be coordinated with a local gastroenterologist, pediatric team, or transplant center?
- What treatments are available if Crohn’s disease returns or worsens after transplant?
Before changing care
Questions for your gastroenterologist
- How stable is my Crohn’s disease now, and how do my activity scores, complications, and treatment history compare with the study’s criteria?
- Are there approved medical or surgical alternatives that remain reasonable for me before considering this transplant study?
- What risks could arise from interrupting, tapering, or changing my current Crohn’s treatment around mobilization and transplant?
- How might my infection history, heart and lung function, blood counts, liver and kidney results, or other conditions affect the risks of this regimen?
- How should my gastroenterology care be coordinated with the transplant and research teams before treatment and during long-term follow-up?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
The objective of this study is to evaluate the safety and effectiveness of administering high-dose chemotherapy followed by infusion of autologous CD34-selected peripheral blood stem cells (PBSC) in pediatric and adult patients with severe Crohn's disease.
Crohn's disease is considered to be an immune-mediated disease of the intestinal tract, typically treated using immune modulating or immune suppressive therapies. These treatments include local anti-inflammatory agents such as 5 aminosalicylic acid products, broad immune suppression using corticosteroids, azathioprine, or methotrexate; cytokine suppression such as antibody against TNFα; IL-12 and antibiotics such as ciprofloxacin and metronidazole that work by decreasing the putative antigen exposure to the intestine. There is little in the literature available on mortality data related to Crohn's Disease, but one series by Farmer et al showed 6% mortality attributable to Crohn's disease. The mortality rate for selective patients with refractory and severe disease is probably higher. This protocol is based on the premise that the sustained inflammation of the GI tract that is characteristic of Crohn's disease is the result of defective mucosal T cell tolerance. The mucosal tolerance is normally maintained by CD4 + T cells characterized as T helper 3 (Th3) and T regulatory 1 (TR1) T cell clones producing TGFβ and IL-10 respectively. There has been much speculation on a possible infectious etiology of IBD implicating primarily mycobacterial organisms, though despite extensive research no pathogenic organisms have definitively been identified. In genetic cytokine knockout animal models of IBD, the typical nonpathogenic enteric flora is sufficient to induce a chronic inflammatory reaction. Autoreactive T cells appear to have broken through the mucosal tolerance with characteristic T helper 1 cytokine profile secreting IL-1 and IFNγ. In theory the most efficient approach to eradicate autoimmune T cell clones is through replacement of the defective immune system with hematopoietic stem cells (HSC) from a healthy allogeneic donor. However, the risks of morbidity and mortality associated with allogeneic HSC transplantation currently do not appear to be justified even in treatment of refractory cases of Crohn's disease. An alternative approach is to use autologous HSC from which potential autoreactive T-cells have been eliminated, based on the hypothesis that from the T-cell depleted autologous graft reconstitution of normal immunity will occur without regeneration of autoimmune clones. Pilot trials in Crohn's and other autoimmune diseases have confirmed the validity of this hypothesis. T-cells in the CD34 selected PBSC product are significantly depleted. If active disease recurs despite intensive immunoablation, it is likely that either CD34 selection did not adequately remove cells responsible for the autoreactive state, or that the emerging genetically predisposed immune system was re-exposed to autoantigens. Unlike allogeneic transplants, the autologous transplant approach has greatly reduced morbidity and mortality due to the absence of graft rejection and graft versus host disease reactions. Currently, autologous HSCT demonstrate that transplant-related mortality is around 5% when transplanted for acute leukemia.
Study design and administration
- Organization
- University of Pittsburgh
- Organization class
- Other
- Organization study ID
- STUDY19100005
- Lead sponsor
- Paul Szabolcs
- Sponsor class
- Other
- Enrollment type
- Estimated
- Allocation
- Na
- Intervention model
- Single Group
- Primary purpose
- Treatment
- Masking
- None
- Who is masked
- Not provided
- Standard age groups
- Child, Adult
Study arms
Experimental
1
High-dose immunotherapy followed by infusion of autologous CD34-selected peripheral blood stem cells (PBSC)
Interventions: Biological: autologous CD34-selected peripheral blood stem cells transplant, Drug: Alemtuzumab, Drug: ATG, Drug: Melphalan, Drug: Thiotepa, Drug: Rituximab, Drug: Cyclophosphamide, Drug: G-CSF, Drug: Mesna
Interventions
Biological
autologous CD34-selected peripheral blood stem cells transplant
high-dose immunotherapy followed by infusion of autologous CD34-selected peripheral blood stem cells (PBSC)
Drug
Alemtuzumab
Transplant conditioning
Drug
ATG
Transplant conditioning
Drug
Melphalan
Transplant conditioning
Drug
Thiotepa
Transplant conditioning
Drug
Rituximab
Transplant conditioning
Drug
Cyclophosphamide
Mobilization
Drug
G-CSF
Mobilization
Drug
Mesna
Mobilization
Eligibility
10 Years–60 Years
All
Not accepted
Inclusion criteria (18)
- Subject and/or guardian must be able to understand and provide informed consent.Registry-derived · unreviewed
- Male or female, 10 through 60 years old, inclusive at time of informed consent.Registry-derived · unreviewed
- Examples of subjects for whom stem cell transplant therapy would be appropriate include, but are not limited to:Registry-derived · unreviewed
- Patients who have had prior surgery and subsequent severe recurrent disease in spite of aggressive maintenance therapy, necessitating consideration of further extensive surgical resections.Registry-derived · unreviewed
- Patients who have diffuse small bowel and colonic disease and who are refractory to aggressive medical treatment, and not eligible for treatment using a surgical approach without the risk of precipitating short bowel syndrome and dependence of parenteral nutrition or who have other conditions that preclude surgeryRegistry-derived · unreviewed
- Patients with a persistently high Harvey Bradshaw Index (HBI) (\>6), CDAI (\>250) or Pediatric CD Activity Index (PCDAI\>45) (44) score or those in the lower, moderate range (HBI ≤ 6), (CDAI \< 250), (PCDAI 30-45), but who are dependent on daily doses of corticosteroids, that are unable to be withdrawn, and aggressive medical treatment to maintain moderate disease status.Registry-derived · unreviewed
- Patients who have resistant complications of CD unresponsive to medical management including multiple enteric fistulas, enterovesicular or enterovaginal fistulas, severe perianal disease, debilitating arthritis, severe skin lesions (pyoderma), and severe bony complications of the disease and therapy (aseptic necrosis, pathologic fractures).Registry-derived · unreviewed
- Patients who developed severe complications to while receiving medical management such as pancreatitis following 6-Mercaptopurine, colitis following 5-ASA or those with severe hypersensitivity to TNFalpha inhibitors (infliximab, adalimumab, certolizumab pegol), anti-integrin agents (natalizumab, vedolizumab) or anti-IL12/23 agents (ustekinumab).Registry-derived · unreviewed
- Patients with stomas are eligible.Registry-derived · unreviewed
- No surgical therapeutic option secondary to risk of short bowel syndrome or patient refusal.Registry-derived · unreviewed
- Harvey Bradshaw Index (HBI) or CD activity score \>5, CDAI \>250 or PCDAI \>30.Registry-derived · unreviewed
- Platelet count greater than 100,000/mm3.Registry-derived · unreviewed
- Absolute neutrophil count greater than 1500/mm3 (unless secondary to 6MP therapy).Registry-derived · unreviewed
- Creatinine ≤ 2.0 mg/dL.Registry-derived · unreviewed
- No history of coronary artery disease; resting LVEF ≥ 40% or shortening fraction ≥ 26%.Registry-derived · unreviewed
- FEV1/FVC ≥ 60% predicted for age; DLCO ≥ 60% predicted value for age.Registry-derived · unreviewed
- Negative pregnancy test for females ≥ 10 years old or who have reached menarche, unless surgically sterilized.Registry-derived · unreviewed
- All females or childbearing potential and sexually active males must agree to use a FDA approved method of birth control for up to 24 months after PBSC transplant or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect.Registry-derived · unreviewed
Exclusion criteria (8)
- Patients who have not been treated with adequate dosing of 6-MP, 5-ASA products and metronidazole.Registry-derived · unreviewed
- Patients who achieved a sustained, corticosteroid free response to anti-TNF alpha therapy, anti-integrin therapy or anti-IL12/23 therapy after a 4 month course of treatment.Registry-derived · unreviewed
- Toxic megacolon, intestinal perforationRegistry-derived · unreviewed
- Conjugated bilirubin \> 2.0 mg/dL.Registry-derived · unreviewed
- Pregnancy or nursing motherRegistry-derived · unreviewed
- HIV/HTLV seropositive, HBsAg, or HCV RNA positive by PCRRegistry-derived · unreviewed
- Active infection, as determined by the appropriate confirmatory testing e.g. blood cultures, PCR testing, etc., within two weeks of mobilization and high dose chemotherapy.Registry-derived · unreviewed
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Number of participants with regimen-related toxicities.
Time frame: From baseline to 24 months post bone marrow transplant
Primary outcome
Number of participants with life-threatening infections.
Time frame: From baseline to 24 months post bone marrow transplant
Primary outcome
Change and duration in the Harvey Bradshaw Index (HBI).
Time frame: Change from Baseline to 24 months post Bone Marrow Transplant
Primary outcome
Change and duration in the Crohn's Disease Activity Index (CDAI).
Time frame: Change from Baseline to 24 months post Bone Marrow Transplant
Primary outcome
Change and duration in the Pediatric Crohn's Disease Activity Index (PCDAI).
Time frame: Change from Baseline to 24 months post Bone Marrow Transplant
Secondary outcome
Number of days it takes for Absolute Neutrophil Count (ANC) to reach greater than 500.
Time frame: 3 consecutive days once ANC is greater than 500.
Secondary outcome
Number of days it takes for Platelet count to reach greater than 20,000/mm3
Time frame: From baseline to 24 months post Bone Marrow Transplant.
Secondary outcome
Number of days it takes for T cell Recovery
Time frame: 24 months post Bone Marrow Transplant
Secondary outcome
Number of participants who have long term cardiac complications
Time frame: 24 months post Bone Marrow Transplant
Secondary outcome
Number of participants who have long term endocrine complications
Time frame: 24 months post Bone Marrow Transplant
Secondary outcome
Number of participants with active advanced Crohn's disease who have immune dysregulation evolution and correction.
Time frame: From Baseline to 24 months post bone marrow transplant
Secondary outcome
Biomarker identification for relapse
Time frame: From baseline to 24 months post bone marrow transplant
Recruiting locations in the United States
Children's Hospital of Pittsburgh of UPMC-Bone Marrow Team
RecruitingPittsburgh, Pennsylvania, 15224, United States
Shawna H McIntyre, RN412-692-5552mcintyresm@upmc.edu
Paul Szabolcs, MD
UPMC Prebyterian- Adult Gastroenterology
RecruitingPittsburgh, Pennsylvania, 15213, United States
David Binion, MD412-383-6968binion@pitt.edu
Beata Pasek, RN412-648-6995BBP10@pitt.edu
Central study contacts
Registry dates
- First posted
- Jun 6, 2008
- Primary completion
- Dec 2026
- Overall completion
- Dec 2027
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.