Autologous Stem Cell Transplantation for Crohn's Disease

NCT00692939 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY19100005
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Crohn's Disease

Keywords

Stem cell transplantation; Crohn's Disease

Outcome Measures

Primary Outcomes (5)

• Number of participants with regimen-related toxicities.

  From baseline to 24 months post bone marrow transplant

• Number of participants with life-threatening infections.

  From baseline to 24 months post bone marrow transplant

• Change and duration in the Harvey Bradshaw Index (HBI).

  Change from Baseline to 24 months post Bone Marrow Transplant

• Change and duration in the Crohn's Disease Activity Index (CDAI).

  Change from Baseline to 24 months post Bone Marrow Transplant

• Change and duration in the Pediatric Crohn's Disease Activity Index (PCDAI).

  Change from Baseline to 24 months post Bone Marrow Transplant

Secondary Outcomes (7)

• Number of days it takes for Absolute Neutrophil Count (ANC) to reach greater than 500.

  3 consecutive days once ANC is greater than 500.

• Number of days it takes for Platelet count to reach greater than 20,000/mm3

  From baseline to 24 months post Bone Marrow Transplant.

• Number of days it takes for T cell Recovery

  24 months post Bone Marrow Transplant

• Number of participants who have long term cardiac complications

  24 months post Bone Marrow Transplant

• Number of participants who have long term endocrine complications

  24 months post Bone Marrow Transplant

Study Arms (1)

1

EXPERIMENTAL

High-dose immunotherapy followed by infusion of autologous CD34-selected peripheral blood stem cells (PBSC)

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

autologous CD34-selected peripheral blood stem cells transplant BIOLOGICAL

high-dose immunotherapy followed by infusion of autologous CD34-selected peripheral blood stem cells (PBSC)

1

Alemtuzumab DRUG

Transplant conditioning

Also known as: Campath-1H

1

ATG DRUG

Transplant conditioning

Also known as: Anti-thymocyte globulin, rabbit; Thymoglobulin

1

Melphalan DRUG

Transplant conditioning

Also known as: L-phenylalanine mustard, phenylalanine mustard, L-PAM, or L-sarcolysin

1

Thiotepa DRUG

Transplant conditioning

1

Rituximab DRUG

Transplant conditioning

Also known as: Rituxan

1

Cyclophosphamide DRUG

Mobilization

Also known as: Cytoxan

1

G-CSF DRUG

Mobilization

Also known as: Neupogen, Granix, Zarxio, Filgrastim

1

Mesna DRUG

Mobilization

1

Eligibility Criteria

• Age: 10 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject and/or guardian must be able to understand and provide informed consent.
• Male or female, 10 through 60 years old, inclusive at time of informed consent.
• Examples of subjects for whom stem cell transplant therapy would be appropriate include, but are not limited to:
• Patients who have had prior surgery and subsequent severe recurrent disease in spite of aggressive maintenance therapy, necessitating consideration of further extensive surgical resections.
• 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 surgery
• 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.
• 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).
• 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).
• Patients with stomas are eligible.
• No surgical therapeutic option secondary to risk of short bowel syndrome or patient refusal.
• Harvey Bradshaw Index (HBI) or CD activity score \>5, CDAI \>250 or PCDAI \>30.
• Platelet count greater than 100,000/mm3.
• Absolute neutrophil count greater than 1500/mm3 (unless secondary to 6MP therapy).
• Creatinine ≤ 2.0 mg/dL.
• No history of coronary artery disease; resting LVEF ≥ 40% or shortening fraction ≥ 26%.

You may not qualify if:

• Patients who have not been treated with adequate dosing of 6-MP, 5-ASA products and metronidazole.
• 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.
• Toxic megacolon, intestinal perforation
• Conjugated bilirubin \> 2.0 mg/dL.
• Pregnancy or nursing mother
• HIV/HTLV seropositive, HBsAg, or HCV RNA positive by PCR
• 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.
• 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.

Sponsors & Collaborators

• Paul Szabolcs: lead

Study Sites (2)

UPMC Prebyterian- Adult Gastroenterology

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC-Bone Marrow Team

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

MeSH Terms

Conditions

Crohn Disease

Interventions

Alemtuzumab; Antilymphocyte Serum; thymoglobulin; Melphalan; Thiotepa; Rituximab; Cyclophosphamide; Granulocyte Colony-Stimulating Factor; Filgrastim; Mesna

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Sera; Biological Products; Complex Mixtures; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Phosphoramide Mustards; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Study Officials

• Paul Szabolcs, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shawna H McIntyre, RN

CONTACT

412-692-5552; mcintyresm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Blood and Marrow Transplantation and Cell Therapy

Study Record Dates

• First Submitted: June 3, 2008
• First Posted: June 6, 2008
• Study Start: June 26, 2012
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)