Intra Arterial (IA) Steroids Infusion for Hepatic Acute Hepatic Graft Versus Host Disease (aGVHD) - Full Text View

Purpose

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.

Condition	Intervention
Acute Graft Versus Host Disease	Drug: Methylprednisolone (Intra-arterial continuous infusion of corticosteroids)

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

Drug Information available for: Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Prednisolone sodium succinate Methylprednisolone sodium succinate

U.S. FDA Resources

Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:

Hepatic response [ Time Frame: 180 days ] [ Designated as safety issue: No ]
The degree to which serum bilirubin levels do or do not decrease

Estimated Enrollment:	30
Study Start Date:	September 2010
Estimated Study Completion Date:	February 2016
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: treatment	Drug: Methylprednisolone (Intra-arterial continuous infusion of corticosteroids) Sedation/anesthesia of patient followed by placement of a 4F vascular sheath and a diagnostic and hepatic angiogram. Angiographic catheter tip to be placed in the proximal proper hepatic artery, secured in place externally and connected to an arterial line pressurized system which allows continuous drip infusion of methylprednisolone diluted in normal saline (600mg/m2 with maximal total dose of 100mg diluted in 480cc in normal saline administered at 20cc/hr for 24 hours).

Arms

Assigned Interventions

Experimental: treatment

Drug: Methylprednisolone (Intra-arterial continuous infusion of corticosteroids)

Sedation/anesthesia of patient followed by placement of a 4F vascular sheath and a diagnostic and hepatic angiogram. Angiographic catheter tip to be placed in the proximal proper hepatic artery, secured in place externally and connected to an arterial line pressurized system which allows continuous drip infusion of methylprednisolone diluted in normal saline (600mg/m2 with maximal total dose of 100mg diluted in 480cc in normal saline administered at 20cc/hr for 24 hours).

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01140984

Contacts

Contact: Michael Y Shapira, MD	00 972 2 6778357	shapiram@hadassah.org.il
Contact: Allan Bloom, MD FSIR	00 972 2 6776502	allan@hadassah.org.il

Locations

Israel
Hadassah Medical Organisation	Recruiting
Jerusalem, Israel, 91120
Contact: Arik Tzukert, DMD 00 972 2 6776095 arik@hadassah.org.il
Contact: Hadas Lemberg, PhD 00 972 2 6777572 lhadas@hadassah.org.il
Principal Investigator: Michael Y Shapira, MD
Principal Investigator: Allan Bloom, MD FSIR

Sponsors and Collaborators

Hadassah Medical Organization

More Information

Publications:

Billaud EM. Clinical pharmacology of immunosuppressive drugs: year 2000--time for alternatives. Therapie. 2000 Jan-Feb;55(1):177-83. Review.

Tanner JE, Alfieri C. Interactions involving cyclosporine A, interleukin-6, and Epstein-Barr virus lead to the promotion of B-cell lymphoproliferative disease. Leuk Lymphoma. 1996 May;21(5-6):379-90. Review. Erratum in: Leuk Lymphoma 2001 Nov-Dec;42(6):following 1447.

Brandenburg U, Gottlieb D, Bradstock K. Antileukemic effects of rapid cyclosporin withdrawal in patients with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. Leuk Lymphoma. 1998 Nov;31(5-6):545-50.

Graziani F, Van Lint MT, Dominietto A, Raiola AM, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Fiorone M, Bruno B, Bacigalupo A. Treatment of acute graft versus host disease with low dose-alternate day anti-thymocyte globulin. Haematologica. 2002 Sep;87(9):973-8.

MacMillan ML, Weisdorf DJ, Davies SM, DeFor TE, Burns LJ, Ramsay NK, Wagner JE, Blazar BR. Early antithymocyte globulin therapy improves survival in patients with steroid-resistant acute graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8(1):40-6.

Tagliabue A, Corti P, Viganò E, Bonanomi S, Uderzo C. Favourable response to antithymocyte globulin therapy in resistant acute graft-versus-host disease. Bone Marrow Transplant. 2005 Sep;36(5):459. No abstract available.

Arai S, Margolis J, Zahurak M, Anders V, Vogelsang GB. Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment. Biol Blood Marrow Transplant. 2002;8(3):155-60.

Khoury H, Kashyap A, Adkins DR, Brown RA, Miller G, Vij R, Westervelt P, Trinkaus K, Goodnough LT, Hayashi RJ, Parker P, Forman SJ, DiPersio JF. Treatment of steroid-resistant acute graft-versus-host disease with anti-thymocyte globulin. Bone Marrow Transplant. 2001 May;27(10):1059-64.

Roy J, McGlave PB, Filipovich AH, Miller WJ, Blazar BR, Ramsay NK, Kersey JH, Weisdorf DJ. Acute graft-versus-host disease following unrelated donor marrow transplantation: failure of conventional therapy. Bone Marrow Transplant. 1992 Jul;10(1):77-82.

Weisdorf D, Haake R, Blazar B, Miller W, McGlave P, Ramsay N, Kersey J, Filipovich A. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood. 1990 Feb 15;75(4):1024-30.

Martin PJ, Schoch G, Fisher L, Byers V, Appelbaum FR, McDonald GB, Storb R, Hansen JA. A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment. Blood. 1991 Apr 15;77(8):1821-8.

Bloom AI, Shapira MY, Or R, Sasson T, Resnick IB, Zilberman I, Verstandig A, Aker M, Slavin S, Muszkat M. Intrahepatic arterial administration of low-dose methotrexate in patients with severe hepatic graft-versus-host disease: an open-label, uncontrolled trial. Clin Ther. 2004 Mar;26(3):407-14.

Sato T, Sakamaki S, Nagaoka Y, Kuribayashi K, Nagamachi Y, Morii K, Honma H, Kogawa K, Kato J, Niitsu Y. Intra-mesenteric artery steroid administration relieved severe refractory gastro-intestinal graft-vs.-host disease in an allogeneic bone marrow transplantation patient. Am J Hematol. 1997 Dec;56(4):277-80.

Nakai K, Tajima K, Tanigawa N, Matsumoto N, Zen K, Nomura S, Fujimoto M, Kishimoto Y, Amakawa R, Sawada S, Fukuhara S. Intra-arterial steroid-injection therapy for steroid-refractory acute graft-versus-host disease with the evaluation of angiography. Bone Marrow Transplant. 2004 Jun;33(12):1231-3.

Responsible Party:	Hadassah Medical Organization
ClinicalTrials.gov Identifier:	NCT01140984 History of Changes
Other Study ID Numbers:	MYS-08-HMO-CTIL
Study First Received:	June 9, 2010
Last Updated:	June 16, 2013
Health Authority:	Israel: Ministry of Health

Keywords provided by Hadassah Medical Organization:

acute graft versus host disease
intra arterial steroid infusion
steroid resistant acute hepatic graft versus host disease

Additional relevant MeSH terms:

Graft vs Host Disease
Immune System Diseases
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics

Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 17, 2013