Acute Graft Versus Host DiseaseNCT01140984
Intra Arterial (IA) Steroids Infusion for Hepatic Acute Hepatic Graft Versus Host Disease (aGVHD)
A study testing Methylprednisolone (Intra-arterial continuous infusion of corticosteroids) in people with Acute Graft Versus Host Disease, run by Hadassah Medical Organization at 1 site in Israel.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Graft Versus Host Disease
- What is being tested?
- Methylprednisolone (Intra-arterial continuous infusion of corticosteroids)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteIsrael
- Study dates
- Sep 2010to Mar 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Acute Graft Versus Host Disease
- Being tested
- Methylprednisolone (Intra-arterial continuous infusion of corticosteroids)
- Keywords
- acute graft versus host disease, intra arterial steroid infusion, steroid resistant acute hepatic graft versus host disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylprednisolone (Intra-arterial continuous infusion of corticosteroids)Drug
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).
| Study group | Role | What they receive |
|---|---|---|
| treatment | Experimental | Not described Receives: Drug: Methylprednisolone (Intra-arterial continuous infusion of corticosteroids) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic response
The degree to which serum bilirubin levels do or do not decrease
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2010 (estimated)
- Study startSep 2010
- Primary completionMar 2015
- Study completionMar 2015
Why it stopped: technical issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Acute Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01140984
- Sponsor's protocol ID
- MYS-08-HMO-CTIL
- Status last verified
- Feb 2011
- First submitted
- 9 Jun 2010
- Last updated
- 21 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Billaud EM. Clinical pharmacology of immunosuppressive drugs: year 2000--time for alternatives. Therapie. 2000 Jan-Feb;55(1):177-83.
PubMed 10860022Tanner 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. doi: 10.3109/10428199609093435.
PubMed 9172802Brandenburg 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. doi: 10.3109/10428199809057613.
PubMed 9922044Graziani 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.
PubMed 12217810MacMillan 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. doi: 10.1053/bbmt.2002.v8.pm11858189.
PubMed 11858189Tagliabue A, Corti P, Vigano 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. doi: 10.1038/sj.bmt.1705065. No abstract available.
PubMed 15980883Arai 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. doi: 10.1053/bbmt.2002.v8.pm11939605.
PubMed 11939605Khoury 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. doi: 10.1038/sj.bmt.1703032.
PubMed 11438821Roy 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.
PubMed 1515883Weisdorf 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.
PubMed 2302454Martin 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.
PubMed 2015405Bloom 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. doi: 10.1016/s0149-2918(04)90036-7.
PubMed 15110133Sato 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. doi: 10.1002/(sici)1096-8652(199712)56:43.0.co;2-6.
PubMed 9395192Nakai 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. doi: 10.1038/sj.bmt.1704523.
PubMed 15094752
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01140984
- Acronym / sponsor ID
- MYS-08-HMO-CTIL
- Conditions
- Acute Graft Versus Host Disease
- Keywords
- acute graft versus host disease, intra arterial steroid infusion, steroid resistant acute hepatic graft versus host disease
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: technical issues
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 10 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Drug: Methylprednisolone (Intra-arterial continuous infusion of corticosteroids) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (13 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Drug | treatment |
Primary outcome
Hepatic response
Time frame: 180 days
The degree to which serum bilirubin levels do or do not decrease
Results and safety
The study was stopped early (reason given: technical issues). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2015.
- Background: PubMed 10860022Billaud EM. Clinical pharmacology of immunosuppressive drugs: year 2000--time for alternatives. Therapie. 2000 Jan-Feb;55(1):177-83.
- Background: PubMed 9172802Tanner 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. doi: 10.3109/10428199609093435.
- Background: PubMed 9922044Brandenburg 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. doi: 10.3109/10428199809057613.
- Background: PubMed 12217810Graziani 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.
- Background: PubMed 11858189MacMillan 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. doi: 10.1053/bbmt.2002.v8.pm11858189.
- Background: PubMed 15980883Tagliabue A, Corti P, Vigano 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. doi: 10.1038/sj.bmt.1705065. No abstract available.
- Background: PubMed 11939605Arai 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. doi: 10.1053/bbmt.2002.v8.pm11939605.
- Background: PubMed 11438821Khoury 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. doi: 10.1038/sj.bmt.1703032.
- Background: PubMed 1515883Roy 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.
- Background: PubMed 2302454Weisdorf 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.
- Background: PubMed 2015405Martin 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.
- Background: PubMed 15110133Bloom 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. doi: 10.1016/s0149-2918(04)90036-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methylprednisolone (Intra-arterial continuous infusion of corticosteroids) in people with Acute Graft Versus Host Disease, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: technical issues). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic response (time frame: 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01140984, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2015.