Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease

NCT01475162 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: MCW-PRO15904
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This trial designed to evaluate the toxicity and efficacy of tocilizumab in the treatment of steroid refractory acute graft versus host disease (GVHD).

Conditions

Acute Graft Versus Host Disease

Keywords

acute Graft versus Host Disease (aGVHD); steroid refractory acute Graft versus Host Disease (aGVHD); chronic Graft versus Host Disease (cGVHD); corticosteroids; allogeneic hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Achieving Complete or Partial Response at Day 56 After Administration of Tocilizumab

  Number of subjects achieving Center for International Blood and Marrow Transplant Research (CIBMTR) score of 0 (complete response); or achieving improvement in one or more organs involved in GVHD without progression in other organs (partial response). CIBMTR score of 0 means no evidence of rash or diarrhea and bilirubin less than 2.0 mg/dl. CIBMTR score of 4 means rash with bullae desquamation, lower gastrointestinal diarrhea more than 1,500 ml, and bilirubin greater than 15.1 mg/dl. Higher score means worse disease.

  Day 56

Secondary Outcomes (7)

• Number of Patients With Partial, Mixed or no GVHD Responses

  Day 56

• GVHD Flares

  Day 90

• Discontinuation of Immunosuppression

  Day 56, Day 180 and Day 365

• Overall Survival

  1 year

• Number of Subjects Experiencing at Least One Serious Adverse Event or Grade 3 Non-serious Adverse Event

  Day 56

Study Arms (1)

Tocilizumab

EXPERIMENTAL

Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response.

Also known as: Actemra

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients age 18 and older who underwent an allogeneic hematopoietic stem cell transplantation.
• Patients are required to have biopsy proven GVHD.
• Patients must have active acute GVHD requiring systemic immune suppressive therapy and that failed or did not respond to first line of therapy.
• First line therapy needs to be a minimum of corticosteroids, methylprednisolone of 1.6mg/kg/day or prednisone of 2mg/kg/day, alone or combined to other agent.
• Failure of GVHD therapy is defined as flare of signs and symptoms of acute GVHD or progression of GVHD grade after at least 72 hours from starting therapy.
• No response to GVHD treatment (corticosteroids ± other agent) after a minimum of 7 days of treatment.
• Patient must be able to give informed consent.

You may not qualify if:

• Intolerance or allergy to Tocilizumab
• Active uncontrolled infection requiring ongoing treatment with antifungals, antibiotics or anti-viral drugs.
• Relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
• Liver enzymes: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 3x upper limit of normal.
• Patients with severe sinusoidal obstruction syndrome who in the judgment of the treating physician are not expected to have normalized bilirubin by day 56 after enrollment.
• Serum bilirubin \> 2x upper limit of normal.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital/Medical College of Wisconsin-Clinical Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Results Point of Contact

• Title: William R. Drobyski
• Organization: Medical College of Wisconsin

wdrobysk@mcw.edu

414-456-4941

Study Officials

• William R Drobyski, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: November 21, 2011
• Study Start: August 8, 2011
• Primary Completion: February 17, 2016
• Study Completion: September 29, 2018
• Last Updated: February 17, 2020
• Results First Posted: January 31, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)