Clinical trial NCT00562497: Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute Graft Versus Host Disease (GVHD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Graft Versus Host Disease
Keywords: Acute GVHD
Acute Graft Versus Host Disease
Lead sponsor: Mesoblast, Ltd.
Sponsor class: INDUSTRY
First posted: 2007-11-22
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants with Treatment Success
timeFrame: 90 Days
Secondary outcomes:
measure: Percentage of Participants with Overall Response
timeFrame: Day 90
measure: 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
timeFrame: Up to Day 56
measure: Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days
timeFrame: Day 14
measure: 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
timeFrame: Up to Day 56
measure: Percentage of Participants with Induction of PR during the first 28 days
timeFrame: Up to Day 28
measure: Time to achieve CR
timeFrame: Up to Day 90
measure: Number of CR per organ
timeFrame: Up to Day 90
measure: Total corticosteroid dose administered
timeFrame: Up to Day 90
measure: Number of corticosteroid-related complications
timeFrame: Up to Day 90
measure: Number of Infectious complications
timeFrame: Up to Day 90
measure: Number of Days of Hospitalization
timeFrame: Up to Day 90
measure: Average Daily Corticosteroid Dose
timeFrame: Up to Day 90
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham (UAB) Hospital
state: Alabama
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: University of California Medical Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Center for Clinical Research
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: St. Francis Cancer Center
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Tufts New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Medical Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Lee's Summit
country: United States
facility: Kansas City Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Jewish Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center, University of Pennsylvania Health System
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Oncology Hematology Association
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Centers
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina(MUSC)
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
city: Herston
country: Australia
facility: Royal Brisbane Hospital
city: Calgary
country: Canada
facility: Peter Lougheed Centre
state: Alberta
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Mesoblast, Inc.
name: Christopher James, PA
role: STUDY_DIRECTOR
References: