Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NST) for Patients With Refractory Crohn's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Northwestern University
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT01288053
First received: January 27, 2011
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

Allogeneic transplantation has been a high-risk procedure, although non-myeloablative conditioning regimens (mini-transplantation) minimizes regimen related toxicity. The investigators, therefore, propose a phase I study of matched sibling allogeneic hematopoietic stem cell transplantation with non-myeloablative conditioning. In addition, graft versus host disease (GVHD) will be virtually eliminated by CAMPATH that removes donor T cells from the graft.

The goal is to assess the toxicity/efficacy (phase I) of allogeneic non-myeloablative hematopoietic stem cell transplantation for high-risk crohn's disease. The primary endpoint to be considered in this study is:

  1. Survival
  2. Duration of disease remission defined as a CDAI < 100. In simplistic terms, this protocol is designed to ablate an aberrant immune system and then, similar to the use of marrow transplants for immunodeficient patients, reconstitute a new immune system with lymphocyte depleted marrow.

PBSC will be mobilized with G-CSF 10 mcg/kg/day (dose may be adjusted down to 5 mcg/kg/day by PI for toxicity, e.g. flu-like symptoms) with stem cell collection beginning on day 4 or 5. Leukapheresis may be repeated up to three consecutive days.Cyclophosphamide 45 mg/kg/day x 4 days will be given IV over 1 hour in 500 cc of normal saline.

Dosage should be based on the lesser of adjusted body weight or actual weight.

CAMPATH-1H 30mg/day x 3 days (no dose adjustment) will be given IV over 2 hours in 100 cc of normal saline. Premedication with acetaminophen 650mg & benadryl 50mg PO/IV will be given 30-60min before infusion. These medications can be repeated as needed.

Fludarabine 25mg/m2 daily for 3 days (no dose adjustment) will be given IV over 30 minutes in 100 cc normal saline.

Hydration approximately 2 liters/m2/day should begin 6 hours before cyclophosphamide and continue until 24 hours after the last cyclophosphamide dose. BID weights will be obtained. Amount of fluid can be modified based on patient's fluid status.

G-CSF will be continued until absolute neutrophil count reaches at least 1,000/ul.

Cyclosporin will be started on day -2 at 200 mg po BID and adjusted by HPLC levels to between 150 - 250 or by toxicity (e.g., tremor, renal insufficiency, TTP, etc.). CSA will be continued for 30 days unless stopped for toxicity or needed to maintain donor engraftment.

Mycophenolate mofetil (MMF)* 1g PO/IV q 12hrs will be started on day -2 and continued for 6 months or longer if needed for engraftment. Then, dosage may be reduced to 250 mg or 500mg q 12hrs for toxicity.

Cyclosporine and MMF guidelines dosage and duration can be modified according to investigators discretion based on side effects, renal function, CBC and GVHD status.


Condition Intervention Phase
Crohn's Disease
Biological: Allogeneic Stem Cell Therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NST) for Patients With Refractory Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Survival [ Time Frame: Five years ] [ Designated as safety issue: Yes ]
    Survival will be measured at 6 months, 1 , 2, 3, 4, and 5 years after transplant.

  • Remission [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Duration of disease remission is defined as a CDAI (Crohn's Disease Activity Index) < 100, and will be measured at 6 months, 1, 2, 3, 4 and 5 years after transplant.


Secondary Outcome Measures:
  • CDAI [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Crohns Disease Activity Index will be measured at 6 months, 1, 2, 3, 4 and 5 years after transplant.Remission is defined as a CDAI < 100,Relapse is defined as a CDAI > 150

  • CCSI [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    CCSI (Craig Crohn's Severity Index) will be performed at 6 months, 1, 2, 3, 4, and 5 years after the transplant.

  • IBDQ [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Inflammatory Bowel Disease Questionnaire (IBDQ)will be performed at 6 months, 1, 2, 3, 4, and 5 years after the transplant.


Estimated Enrollment: 20
Study Start Date: January 2010
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogeneic Stem Cell Therapy
Allogeneic Stem Cell Therapy will be performed after conditioning
Biological: Allogeneic Stem Cell Therapy
Donor stem cells will be given to subject diagnosed with Crohn's disease

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >18 years and less than age 45 years at time of pretransplant evaluation and,
  2. Ability to give informed consent.

And either A or B A)An established clinical diagnosis of severe CD with disease onset before 16 years old (at least 71 genetic loci predispose to pediatric CD, Limbergen, JV. Annu. Rev. Genom. Human Genet. 2009; 10:89-116) that has failed therapy with prednisone, 5 ASA products and has failed an anti-TNF therapy. Failure is defined as a CDAI (appendix A) 250-400 or a Craig Severity Score that is > 17 (appendix C).

B)Relapse after an autologous HSCT with a CDAI (appendix A) 250-400 or a Craig Severity Score that is > 17 (appendix C).

C)A diagnosis of CD with NOD mutation and CDAI 250-400 or CSI >17 despite anti-TNF therapy.

Exclusion Criteria:

  1. HIV positive.
  2. History of coronary artery disease, or congestive heart failure.
  3. Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy.
  4. Prior history of malignancy except localized basal cell or squamous skin cancer. 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
  5. Positive pregnancy test, lactation, inability or unwillingness to pursue effective means of birth control, failure to accept or comprehend irreversible sterility as a side effect of therapy.
  6. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
  7. FEV 1/FVC < 50% of predicted, DLCO < 50% of predicted.
  8. Resting LVEF < 50%.
  9. Bilirubin > 2.0 mg/dl, transferase (AST) > 2x upper limit of normal, unless the abnormalities are secondary to Crohn's disease.
  10. Serum creatinine > 2.0 mg/dl.
  11. Platelet count less than 100,000/ul, ANC less than 1500/ul.
  12. Patients presenting with intestinal perforation or toxic megacolon, or a suppurative problem that will require urgent surgery. In addition, the patient may not have any active infection. The presence of intestinal stomas does not exclude the patient from study.
  13. Pre-study peripheral blood counts must include a platelet count greater than 100,000/ul and an absolute neutrophil count greater than 1500/ul.
  14. No available HLA matched sibling or HLA matched cord blood unit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01288053

Contacts
Contact: Dzemila Spahovic, MD 312-695-4960 d-spahovic@northwestern.edu

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Richard Burt, MD         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Richard Burt, MD Northwestern University
  More Information

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT01288053     History of Changes
Other Study ID Numbers: DIADCDAllo2005
Study First Received: January 27, 2011
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on July 24, 2014