Crohn's Allogeneic Transplant Study (CATS)
|ClinicalTrials.gov Identifier: NCT01570348|
Recruitment Status : Suspended (Temporarily closed to enrollment)
First Posted : April 4, 2012
Last Update Posted : August 4, 2017
|Condition or disease||Intervention/treatment||Phase|
|Crohn Disease||Procedure: Allogeneic Bone Marrow Transplantation Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Drug: Mycophenolic Acid Other: Quality-of-Life Assessment Drug: Tacrolimus Radiation: Total-Body Irradiation||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Allogeneic Hematopoietic Cell Transplantation for Patients With Treatment-Refractory Crohn's Disease: A Phase 2 Study|
|Study Start Date :||July 2012|
|Estimated Primary Completion Date :||February 2018|
|Estimated Study Completion Date :||February 2022|
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.
Procedure: Allogeneic Bone Marrow Transplantation
Undergo allogeneic BMT
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Drug: Mycophenolic Acid
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Given IV or PO
Radiation: Total-Body Irradiation
- Event-free survival (EFS) [ Time Frame: At 1 year post-transplant ]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.
- Development of infectious complications [ Time Frame: Up to 5 years ]The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient.
- Disease activity [ Time Frame: Up to 5 years ]Evaluated using a standardized tool for evaluating CD (CDAI).
- EFS [ Time Frame: Up to 5 years post-transplant ]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.
- Incidence and severity of GVHD [ Time Frame: Up to 5 years ]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 ]Includes the administration of any therapy (drugs, biologics, or any other treatments) clearly given as immunomodulatory therapy for underlying CD.
- Incidence of graft rejection [ Time Frame: Up to 5 years ]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.
- Overall survival [ Time Frame: Time of treatment assignment until death due to any cause, assessed up to 5 years ]Characterized by the event rates as functions of all patients enrolled and at risk of the event, with exact confidence intervals.
- Quality of life measured using the previously validated Short Inflammatory Bowel Disease Questionnaire [ Time Frame: Up to 5 years ]
- 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 ]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.
- Treatment-related mortality (TRM) [ Time Frame: Time from BMT to death definitely or probably resulting from treatment, assessed up to 5 years ]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%.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01570348
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||George Georges||Fred Hutch/University of Washington Cancer Consortium|