Intra Arterial (IA) Steroids Infusion for Hepatic Acute Hepatic Graft Versus Host Disease (aGVHD)

Acute Graft Versus Host Disease Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01140984
• Other study ID #: MYS-08-HMO-CTIL
• Status: Terminated
• Phase: N/A
• First received: June 9, 2010
• Last updated: April 19, 2015
• Start date: September 2010
• Est. completion date: March 2015

Study information

• Verified date: February 2011
• Source: Hadassah Medical Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Graft Versus Host Disease
• Graft vs Host Disease

Intervention

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).

Locations

Country	Name	City	State
Israel	Hadassah Medical Organisation	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

References & Publications (14)

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hepatic response	The degree to which serum bilirubin levels do or do not decrease	180 days	No