Infliximab and Basiliximab for Treatment of Steroid Refractory Acute Graft Versus Host Disease

NCT01485055 | Terminated Phase 2 Results DMC

• 1 other identifier: NCH-IRB11-00659
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

Acute Graft Versus Host Disease (GVHD) is a serious medical condition that is a common development after Bone Marrow Transplant (BMT). Acute GVHD happens when the donor cells attack and damage your tissues and organs after transplant. Acute GVHD often causes: Skin rashes, nausea, vomiting, abdominal pain, diarrhea (may have blood), liver damage that can cause inflammation in the liver or jaundice (yellowing of the skin or eyes), damage to other organs Steroids are the first line of treatment for acute GVHD. About a quarter of the patients that develop acute GVHD may not respond to steroid and have steroid refractory GVHD (SR-aGVHD). Patients with SR-aGVHD may need other medications. SR-aGVHD, is a potentially life threatening condition. There is no standard treatment and it may not respond to treatment. The goals of this study are to find out if Infliximab and basiliximab can treat SR-aGVHD. Participants in this study will receive combination therapy (2 drugs: infliximab and basiliximab) once a week for four weeks.

Conditions

Graft Versus Host Disease; Steroid Refractory GVHD; Acute GVH Disease

Keywords

aGVHD; GVHD; Graft versus host disease; Acute graft versus host disease; Steroid refractory graft versus host disease; Bone marrow transplant; BMT; HSCT; infliximab; basiliximab; Monoclonal antibody treatment

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate Determination

  Complete response was defined as complete resolution of all signs and symptoms of GvHD in all organs using the Modified Glucksberg grading of acute graft versus host disease scale. The score used for GvHD grading complete response was "0" in all evaluable organs.

  28 days

Study Arms (1)

Infliximab and Basiliximab

EXPERIMENTAL

Other Names: Simulect Remicade Monoclonal antibody Participants in this research study will receive combination therapy (2 drugs: Infliximab and Basiliximab)once a week for four weeks. Both drugs will be given through the participant's broviac, port or through a vein in the arm. It will take about 4-5 hours to complete the 2-drug combination therapy each week. Participants will be given pre-medications to help prevent reactions to the study drugs. Infliximab will be given at a dose of 10mg per Kg per dose. Basiliximab will be given in 10mg doses to patients who weigh less than 35kg. Patients who weigh weigh more than 35kg will receive 20mg doses. Patients will receive both drugs weekly on days 1,8,15 and 22. Each drug will be given 4 times.

Drug: Infliximab and Basiliximab

Interventions

Infliximab and Basiliximab DRUG

Participants in this research study will receive combination therapy (2 drugs: Infliximab and Basiliximab)once a week for four weeks. Both drugs will be given through the participant's broviac, port or through a vein in the arm. It will take about 4-5 hours to complete the 2-drug combination therapy each week. Participants will be given pre-medications to help prevent reactions to the study drugs. Infliximab will be given at a dose of 10mg per Kg per dose. Basiliximab will be given in 10mg doses to patients who weigh less than 35kg. Patients who weigh weigh more than 35kg will receive 20mg doses. Patients will receive both drugs weekly on days 1,8,15 and 22. Each drug will be given 4 times.

Also known as: Simulect, Remicade, Monoclonal antibody

Infliximab and Basiliximab

Eligibility Criteria

• Age: 6 Months - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient with either progressive aGvHD or Steroid Refractory aGvHD after Bone marrow transplant
• Prophylactic GvHD therapy with cyclosporine, tacrolimus, MMF, or sirolimus can be continued.
• Patients with late onset acute GvHD will be eligible
• Patients should have an absolute neutrophil count (ANC) of \>500µL
• Patients with renal dysfunction or veno-occlusive disease are eligible

You may not qualify if:

• Patient should not be getting any other experimental therapy for aGvHD
• Patients with active uncontrolled life threatening infection (s) from viral, bacterial, fungal or other organisms will be excluded. Patients with HIV infection will be excluded
• Patients who are pregnant, breast feeding, or if sexually active and unwilling to use effective birth control for the duration of this study will be excluded
• Patients with NYHA Class III or IV heart failure will be excluded

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (3)

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Methodist Healthcare System of San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Srinivasan R, Chakrabarti S, Walsh T, Igarashi T, Takahashi Y, Kleiner D, Donohue T, Shalabi R, Carvallo C, Barrett AJ, Geller N, Childs R. Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis. Br J Haematol. 2004 Mar;124(6):777-86. doi: 10.1111/j.1365-2141.2004.04856.x.

  PMID: 15009066 BACKGROUND

• Rao K, Rao A, Karlsson H, Jagani M, Veys P, Amrolia PJ. Improved survival and preserved antiviral responses after combination therapy with daclizumab and infliximab in steroid-refractory graft-versus-host disease. J Pediatr Hematol Oncol. 2009 Jun;31(6):456-61. doi: 10.1097/MPH.0b013e31819daf60.

  PMID: 19648797 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Infliximab; Basiliximab; Antibodies, Monoclonal

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized

Results Point of Contact

• Title: Rajinder Bajwa
• Organization: Nationwide Childrens Hospital

rajinder.bajwa@nationwidechildrens.org

6147222000

Study Officials

• Rajinder S Bajwa, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Rajinder.P.S. Bajwa, MBBS, MD, MRCP Assitant Professor of Pediatrics at Ohio State University Department of Hematology/Oncology/BMT

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 5, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: September 26, 2016
• Last Updated: April 5, 2019
• Results First Posted: April 5, 2019

Record last verified: 2019-04

Locations

US (3)