Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute Graft Versus Host Disease (GVHD)

Graft Versus Host Disease Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute GVHD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00562497
• Other study ID #: 265
• Status: Completed
• Phase: Phase 3
• Start date: January 31, 2008
• Est. completion date: May 20, 2010

Study information

• Verified date: January 2022
• Source: Mesoblast, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of Prochymal® versus placebo in combination with corticosteroids as initial therapy for acute GVHD. Corticosteroids have been the primary therapy for patients with previously untreated acute GVHD and the historical published data define an expected 35% complete response (CR) at Day +28 using this therapy.

Description:

Participants will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. The first infusion of the investigational product (IP) will be administered within 72 hours of the start of systemic corticosteroid therapy. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Participants assigned to the active treatment group will receive Prochymal®. Participants assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all participants receive all six infusions. The discontinuation of investigational agent is allowed for GVHD worsening with subsequent need for salvage therapy. All infusions must be given at least 3 days apart.

Participants will be evaluated for efficacy and safety until death, withdrawal or 90 study days after randomization, whichever occurs first. Study will be unblinded and data analyzed at Day 90 post 1st infusion (Day 0) following final participant enrollment. Participants will be followed for safety for 12 months post 1st infusion (Day 0).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: May 20, 2010
• Est. primary completion date: July 14, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Participants must be 18 years to 70 years of age, inclusive

• Participants must have received an allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or cord blood or administered a donor leukocyte infusion.

• Participants must have newly diagnosed Grades B-D acute GVHD. Biopsy confirmation of GVHD is strongly recommended but not required. Randomization should not be delayed awaiting biopsy or pathology results.

• Participants must be randomized and treated with corticosteroid (1-2 mg/kg/d methylprednisolone, or equivalent) and Prochymal®/placebo within 72 hours of onset of acute GVHD.

• Participants must have adequate renal function as defined by: Calculated Creatinine Clearance of >30 mL/min using the Cockcroft-Gault equation

• Participants who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male participants must use adequate contraception

• Participant must have a minimum Karnofsky Performance Level of at least 30 at the time of study entry

• Participant (or legal representative where appropriate) must be capable of providing written informed consent.

Exclusion Criteria:

• Participant has been previously treated with systemic immunosuppressive therapy for acute GVHD

• Participant has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant including uncontrolled infection, heart failure, pulmonary hypertension, etc.

• Participants may not receive any other investigational agents (not approved by the FDA for any indication) concurrently during study participation or within 30 days of randomization.

• Participant has a known allergy to bovine or porcine products or dimethyl sulfoxide (DMSO)

• Participant has received a transplant for a solid tumor disease.

• Participant requires more than 2 liters/min of oxygen to maintain stable oxygen saturation (Sa02) greater than or equal to 92%

• Participant requires a renal dopamine dose greater than 1-3 mcg/kg/min to maintain renal blood flow associated with renal failure and improved urinary output.

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Prochymal®
Prochymal® intravenous infusion.

Other:
• Placebo
Placebo-matching Prochymal® intravenous infusion.
• Corticosteroid
Administration will be intravenously as prescribed by the caregiver.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	St. Vincent's Hospital	Darlinghurst
Australia	Royal Brisbane Hospital	Herston
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Emory University	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	University of Alabama Birmingham (UAB) Hospital	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts New England Medical Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	Medical University of South Carolina(MUSC)	Charleston	South Carolina
United States	Northwestern Center for Clinical Research	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Hospitals	Chicago	Illinois
United States	Jewish Hospital	Cincinnati	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Health System	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	St. Francis Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Kansas City Cancer Center	Lee's Summit	Missouri
United States	UCLA Medical Center	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Loyola University Medical Center	Maywood	Illinois
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	New York Presbyterian Hospital	New York	New York
United States	Abramson Cancer Center, University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Oncology Hematology Association	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Centers	Pittsburgh	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Medical Center	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Texas Transplant Institute	San Antonio	Texas
United States	University of California Medical Center	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Mesoblast, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Treatment Success	Treatment was considered a success if all of the following conditions were met: Achieved induction of a complete response (CR) within 28 days after first infusion; CR followed by 28 days maintenance of a clinically meaningful response defined as the response that did not require an increase in corticosteroid dose (methylprednisolone doses >2 milligram/kilogram/day [mg/kg/d] or prednisone doses >2.5 mg/kg/d) for more than 7 consecutive days; Did not require second line/escalation therapy through Study Day 56; and survived 90 study days.	90 Days
Secondary	Percentage of Participants with Overall Response	Overall Response was defined as participants who achieved complete response or partial response (CR+PR).	Day 90
Secondary	Percentage of Participants with Induction of a 2-grade decrease in (Graft Versus Host Disease) GVHD by Study Day 28 with maintenance of a 2-grade decrease in GVHD through Study Day 56		Up to Day 56
Secondary	Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days		Day 14
Secondary	Percentage of Participants with Induction of a CR after Study Day 28 and clinically managed with steroids with second line/escalation therapy through Study Day 56		Up to Day 56
Secondary	Percentage of Participants with Induction of PR during the first 28 days		Up to Day 28
Secondary	Time to achieve CR		Up to Day 90
Secondary	Number of CR per organ		Up to Day 90
Secondary	Total corticosteroid dose administered		Up to Day 90
Secondary	Number of corticosteroid-related complications	Corticosteroid-related complications included hyperglycemia requiring insulin, corticosteroid myopathy and psychosis.	Up to Day 90
Secondary	Number of Infectious complications	Infectious complications included viral, fungal or bacterial complications.	Up to Day 90
Secondary	Number of Days of Hospitalization		Up to Day 90
Secondary	Average Daily Corticosteroid Dose		Up to Day 90

External Links

•   Click here for more information about this study: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed