Clinical trial NCT01140984: Intra Arterial (IA) Steroids Infusion for Hepatic Acute Hepatic Graft Versus Host Disease (aGVHD)
Official title: An Investigator Initiated Open Study to Evaluate the Efficacy and Safety of Intra Arterial Infusion for Treatment of Steroid Resistant Acute Hepatic Graft Versus Host Disease (AGVHD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Graft Versus Host Disease
Keywords: acute graft versus host disease
intra arterial steroid infusion
steroid resistant acute hepatic graft versus host disease
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2010-06-10
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Post allogeneic hematopoietic stem cell transplantation (HSCT) patients with steroid resistant acute GVHD localised to the liver will receive 24 hours continuous intra-arterial infusion of methylprednisolone.

Detailed description: The study population will include 30 patients with SR AGVHD having an index of B, C, or D on the IBMTR severity index localized to the liver.

Standard treatment for SR AGVHD includes: IV cyclosporine or tacrolimus with adjusted doses depending on serum levels and methylprednisolone or prednisone 2 mg/kg/d. This treatment may be continued during the study period although steroid taper down should be attempted if clinically possible.

GVHD diagnosis will be based upon clinical criteria and biopsy (if needed) from an involved organ. GVHD will be graded according to the International Bone Marrow Transplantation Registry (IBMTR) severity index.

Intra-arterial treatment should be given in less than 72h from completion of inclusion criteria.

Partially responding or non-responding patients may receive a second treatment within 14 days of the initial intra-arterial treatment, at the discretion of the treating physician.

Definitions

Hepatic response:

* Initial response - the day in which bilirubin level began to decrease.
* Partial response 75 - the day in which bilirubin level decreased below 75% of basal level.
* Partial response 50 - the day in which bilirubin level decreased below 50% of basal level.
* Partial response 25 - the day in which bilirubin level decreased below 25% of basal level.
* Complete response - the day in which bilirubin level decreased to normal level.

Eligibility criteria: Inclusion Criteria:

* Recipient of allogeneic stem cell transplantation.
* Age\>18 years.
* Post stem cells transplant \<100 days.
* AGVHD of liver, IBMTR index B, C, D.
* Resistant AGVHD - Patients will be eligible for inclusion if they developed grade B-D AGVHD with progression after 3 days standard treatment OR unresponsive to at least 7 days standard treatment OR incomplete response to standard treatment after 14 days.
* Has received no 1st line treatment for steroid refractory AGVHD.
* Signed a written informed consent

Exclusion Criteria:

* Not fulfilling any of the inclusion criteria.
* Active life-threatening infection.
* Inability to comply with study requirements.
* Inability to give informed consent.
* Contraindication to arterial catheterization (uncorrectable coagulopathy, severe allergic reaction to contrast material or others).
* Inability to give the first Intra-arterial treatment in less than 72h from completion of inclusion criteria
* An IBMTR index ≤ A.
* Refractory skin AGVHD or severe diarrhea..
* Pregnant or breast-feeding female or childbearing potential.
* Known to be HIV positive.
* Has been diagnosed with veno-occlusive disease.
* Has been diagnosed with multi organ failure.
* Known renal failure eGFR \<30

Primary outcomes:
measure: Hepatic response
timeFrame: 180 days
Secondary outcomes:
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Organisation
Study officials:
References:
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