Ignite Creation Date:
2024-05-05 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00146978
Status:
COMPLETED
Last Update Posted:
2006-11-07
First Post:
2005-09-04
Brief Title:
Intra-Arterial Catheter Directed Therapy for Severe Graft vs Host Disease GVHD
Sponsor:
Hadassah Medical Organization
Organization:
Hadassah Medical Organization
Study Overview
Official Title:
A Phase 12 Study to Evaluate Intra-Arterial Catheter Directed Therapy for Severe Gastro-Intestinal andor Hepatic Graft vs Host Disease GVHD
Status:
COMPLETED
Status Verified Date:
2006-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Graft versus host disease GVHD is a major complication of allogeneic bone marrow transplantation BMT resulting in death in the majority of steroid resistant patients The study was designed to assess the efficacy of regional intra-arterial treatment in patients with resistant hepatic andor gastro-intestinal GVHD
Detailed Description:
Graft versus host disease GVHD is the most ominous side effect of allogeneic bone marrow or blood stem cell transplantation BMT GVHD causes a severe inflammatory process which affects primarily the skin and the GI system including the liver Pharmacological treatment of GVHD includes various immunosuppressive and immune-modulating drugs including steroids cyclosporin tacrolimus methotrexate and anti-lymphocyte agents These agents can aggravate immunologic incompetence exposing the patient to infections and secondary malignancy as well as reducing the efficacy of graft versus leukemia graft versus tumor GVL GVT effects induced by alloreactive donor lymphocytes In spite of this effect on the immune system only 50-70 of the patients achieve partial control of GVHD which can rapidly deteriorate and result in death Despite the use of innovative immunosuppressive modalities the prognosis of steroid resistant GVHD is usually poor GVHD can be mostly localized to a specific organ skin liver GI with liver involvement tending to be more chronic and resistant The bile ducts are the main target for GVHD with their blood supply originating from the hepatic artery This may explain the ineffective nature of oral steroids absorbed through the gut into the portal vein
Sato et al reported that an infusion of steroids to the superior and inferior mesenteric arteries induced remission in a patient with refractory GI GVHD This method has never been tested in patients with fulminant liver GVHD We decided to test this approach in a larger cohort of patients with steroid resistant hepatic and intestinal GVHD
Patients were eligible for inclusion if they developed grade 3-4 hepatic andor GI GVHD unresponsive to treatment with IV cyclosporin 3 mgkg and IV methylprednisolone MP 2 mgkg GVHD diagnosis was based upon clinical criteria and in some of the patients supported by biopsy GVHD grading was graded according to the Seattle severity index
Patients with hepatic GVHD were first treated with slow intra-arterial hepatic artery infusion of methotrexate Pharmachemie Netherland 10mgm2 and MP Pharmacia and Upjohn Belgium 75mgm2 The protocol was later on changed with the exclusion of methotrexate and increase of MP dose to 1000mg
Patients with GI GVHD were treated with intra-arterial SMA IMA infusion of MP 40-60 mgvessel In cases of upper GI GVHD intra-arterial infusion of MP was given to the gastro-duodenal artery GDA Later on injections to the internal iliacs were added
Technique Angiography was performed using standard sterile technique local anesthesia with lidocaine 1 and conscious intravenous sedation Visceral arteriography was performed in order to determine anatomy and identify variant arterial blood supply to the gut A selection of 3 - 5 Fr angiographic catheters was used at the discretion of the angiographer performing the procedure The most frequently used catheters were 4 Fr 5 Fr Cobra 2 and Rim catheters Cook Inc Bloomington In Other catheters used included the Sos 2 Angiodynamics Inc Queensbury NY and the 3Fr Terumo SP co-axial catheter Terumo Europe NV Leuven Belgium Once the catheter was in position each drug was injected into the artery over approximately three minutes After completion of the procedure the catheter was removed and direct manual pressure over the arteriotomy maintained until hemostasis was achieved Patients remained on complete bed rest with the involved extremity extended for 6 hours in accordance with standard angiographic practice Compression devices were not used
Definitions Hepatic response initial response - the day in which bilirubin level began to decrease partial response - the day in which bilirubin level decreased below 70 of basal level complete response - the day in which bilirubin level decreased below 30 of basal level
GI response initial response - the day in which symptom amelioration appeared diarrhea volume and abdominal pain Complete response - the day in which symptoms resolved
Sato et al reported that an infusion of steroids to the superior and inferior mesenteric arteries induced remission in a patient with refractory GI GVHD This method has never been tested in patients with fulminant liver GVHD We decided to test this approach in a larger cohort of patients with steroid resistant hepatic and intestinal GVHD
Patients were eligible for inclusion if they developed grade 3-4 hepatic andor GI GVHD unresponsive to treatment with IV cyclosporin 3 mgkg and IV methylprednisolone MP 2 mgkg GVHD diagnosis was based upon clinical criteria and in some of the patients supported by biopsy GVHD grading was graded according to the Seattle severity index
Patients with hepatic GVHD were first treated with slow intra-arterial hepatic artery infusion of methotrexate Pharmachemie Netherland 10mgm2 and MP Pharmacia and Upjohn Belgium 75mgm2 The protocol was later on changed with the exclusion of methotrexate and increase of MP dose to 1000mg
Patients with GI GVHD were treated with intra-arterial SMA IMA infusion of MP 40-60 mgvessel In cases of upper GI GVHD intra-arterial infusion of MP was given to the gastro-duodenal artery GDA Later on injections to the internal iliacs were added
Technique Angiography was performed using standard sterile technique local anesthesia with lidocaine 1 and conscious intravenous sedation Visceral arteriography was performed in order to determine anatomy and identify variant arterial blood supply to the gut A selection of 3 - 5 Fr angiographic catheters was used at the discretion of the angiographer performing the procedure The most frequently used catheters were 4 Fr 5 Fr Cobra 2 and Rim catheters Cook Inc Bloomington In Other catheters used included the Sos 2 Angiodynamics Inc Queensbury NY and the 3Fr Terumo SP co-axial catheter Terumo Europe NV Leuven Belgium Once the catheter was in position each drug was injected into the artery over approximately three minutes After completion of the procedure the catheter was removed and direct manual pressure over the arteriotomy maintained until hemostasis was achieved Patients remained on complete bed rest with the involved extremity extended for 6 hours in accordance with standard angiographic practice Compression devices were not used
Definitions Hepatic response initial response - the day in which bilirubin level began to decrease partial response - the day in which bilirubin level decreased below 70 of basal level complete response - the day in which bilirubin level decreased below 30 of basal level
GI response initial response - the day in which symptom amelioration appeared diarrhea volume and abdominal pain Complete response - the day in which symptoms resolved
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None