Crohn's Allogeneic Transplant Study (CATS)
This phase II trial studies how well giving a donor bone marrow transplant (BMT) works in treating patients with refractory Crohn's Disease. We will select patients with severe Crohn's Disease and active inflammation despite the best medical and surgical treatments. These patients must be healthy enough to undergo a transplantation procedure. They cannot have an active infection, and their heart, lungs, kidneys, and liver cannot be failing. The transplant procedure starts with chemotherapy and a small dose of radiation, to weaken a patient's immune system so that it will accept bone marrow cells from another person. After that other person's bone marrow cells are given to the patient, immune suppressive medicines are given to prevent the new cells from being rejected and to stop those cells from damaging the patient. After the new donor cells start to work, blood counts will rise and the new immune system will start to grow. During this time, there is a risk of infection. Antibiotics and anti-viral drugs will be given to prevent infection. When the new donor cells are well-established, immune suppressive medicines are discontinued. We will examine parts of the intestine that were inflamed before the start of the transplant procedure, to be sure the Crohn's Disease has disappeared after the transplant. Patients will be formally evaluated for Crohn's activity at around 100 days after transplant, and yearly after that for 5 years.
Drug: fludarabine phosphate
Radiation: total-body irradiation
Procedure: allogeneic bone marrow transplantation
Drug: mycophenolic acid
Drug: mycophenolate mofetil
Other: quality-of-life assessment
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Hematopoietic Cell Transplantation for Patients With Treatment-Refractory Crohn's Disease: A Phase 2 Study|
- Event-free survival (EFS) [ Time Frame: At 1 year post-transplant ] [ Designated as safety issue: No ]Defined as alive and free of active CD. Described graphically using a Kaplan-Meier estimate. Generated with confidence intervals using Greenwood's formula to calculate the standard error. Estimated with exact 90% confidence intervals.
- EFS [ Time Frame: Up to 5 years post-transplant ] [ Designated as safety issue: No ]Described graphically using a Kaplan-Meier estimate. Generated with confidence intervals using Greenwood's formula to calculate the standard error. Estimated with exact 90% confidence intervals.
- Overall survival [ Time Frame: Time of treatment assignment until death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]Characterized by the event rates as functions of all patients enrolled and at risk of the event, with exact confidence intervals.
- Treatment-related mortality (TRM) [ Time Frame: Time from BMT to death definitely or probably resulting from treatment, assessed up to 5 years ] [ Designated as safety issue: No ]A stopping rule will be imposed for TRM occurring within one year of transplant. The study will be stopped if at any point there is moderately strong evidence that the rate of TRM exceeds 10%. Moderately strong evidence will be taken to mean that the lower bound of a one-sided 80% confidence interval for the true rate of TRM is above 10%.
- Regimen-related toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4 [ Time Frame: Up to 1 year post-BMT ] [ Designated as safety issue: Yes ]Characterized by the rates of reportable events as functions of all patients enrolled and at risk of the event, with exact confidence intervals. With the exception of adverse events (AEs) that are universal and expected following conditioning therapy, all reportable AEs will be tabulated for each patient from the time that the subject starts mobilization of hematopoietic cells until day +365 after transplant.
- Development of infectious complications [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient.
- Quality of life measured using the previously validated Short Inflammatory Bowel Disease Questionnaire [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Disease activity [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Evaluated using a standardized tool for evaluating CD (CDAI).
- Incidence of graft rejection [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Engraftment is defined as achieving > 5% donor peripheral blood CD3 T cell chimerism by day 84 after HCT. Primary graft failure is defined as a donor peripheral blood CD3 T cell chimerism peak of < 5% by Day 84 post-HCT. Secondary graft failure is defined as documented engraftment followed by loss of the graft with donor peripheral blood CD3 T cell chimerism < 5% as demonstrated by a chimerism assay.
- Incidence and severity of GVHD [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The grading of acute and chronic GVHD will follow previously published guidelines but will also include capture of symptoms and characterization of alternative causes. The highest level of organ abnormalities, the etiologies contributing to the abnormalities and biopsy results pertaining to GVHD will be identified. Since both GVHD and CD involve the gastrointestinal tract, all diagnostic biopsies of these organs will be reviewed by pathologists experienced in the diagnosis of GVHD and IBD, respectively.
- Incidence of disease-modifying drugs for CD initiated post-transplant [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Includes the administration of any therapy (drugs, biologics, or any other treatments) clearly given as immunomodulatory therapy for underlying CD.
|Study Start Date:||July 2012|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (allogeneic BMT)
CONDITIONING THERAPY: Patients receive fludarabine phosphate IV over 30-60 minutes QD on days -6 to -2 and cyclophosphamide IV over 1-2 hours QD on days -6 and -5. Patients undergo total body irradiation on day -1.
TRANSPLANTATION: Patients undergo donor BMT on day 0.
IMMUNOSUPPRESSIVE THERAPY: Patients receive high-dose cyclophosphamide IV over 1-2 hours QD on days 3-4, tacrolimus IV daily or PO BID on days 5-180 with taper to day 365, and mycophenolate acid enteric coated or mycophenolate mofetil PO TID on days 0-35.
Drug: fludarabine phosphate
Other Names:Drug: cyclophosphamide
Other Names:Radiation: total-body irradiation
Other Name: TBIProcedure: allogeneic bone marrow transplantation
Undergo allogeneic BMT
Other Names:Drug: tacrolimus
Given IV or PO
Other Names:Drug: mycophenolic acid
Other Names:Drug: mycophenolate mofetil
Other Names:Other: quality-of-life assessment
Other Name: quality of life assessmentOther: laboratory biomarker analysis
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01570348
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||George McDonald||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|