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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2011 by Hadassah Medical Organization
Sponsor:
Information provided by (Responsible Party):
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT01140984
First received: June 9, 2010
Last updated: June 16, 2013
Last verified: February 2011
  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:


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).

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:

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
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 15, 2014