Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute Graft Versus Host Disease (GVHD)
- Conditions
- Graft Versus Host Disease
- Interventions
- Drug: Prochymal®Other: PlaceboOther: Corticosteroid
- Registration Number
- NCT00562497
- Lead Sponsor
- Mesoblast, Inc.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 192
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prochymal® 2x10^6 hMSC/kg Prochymal® Participants will receive 6 infusions of Prochymal® 2x10\^6 human mesenchymal stem cells (hMSC)/kg IV during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28. Prochymal® 2x10^6 hMSC/kg Corticosteroid Participants will receive 6 infusions of Prochymal® 2x10\^6 human mesenchymal stem cells (hMSC)/kg IV during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28. Placebo Placebo Participants will receive 6 infusions of placebo-matching Prochymal® intravenously (IV) during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28. Placebo Corticosteroid Participants will receive 6 infusions of placebo-matching Prochymal® intravenously (IV) during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Treatment Success 90 Days 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Overall Response Day 90 Overall Response was defined as participants who achieved complete response or partial response (CR+PR).
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 Percentage of Participants with Induction of PR during the first 28 days Up to Day 28 Number of Infectious complications Up to Day 90 Infectious complications included viral, fungal or bacterial complications.
Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days Day 14 Number of corticosteroid-related complications Up to Day 90 Corticosteroid-related complications included hyperglycemia requiring insulin, corticosteroid myopathy and psychosis.
Average Daily Corticosteroid Dose Up to Day 90 Time to achieve CR Up to Day 90 Total corticosteroid dose administered Up to Day 90 Number of Days of Hospitalization Up to Day 90 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 Number of CR per organ Up to Day 90
Trial Locations
- Locations (53)
University of Chicago Hospitals
🇺🇸Chicago, Illinois, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Oncology Hematology Association
🇺🇸Pittsburgh, Pennsylvania, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Northwestern Center for Clinical Research
🇺🇸Chicago, Illinois, United States
Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Kansas City Cancer Center
🇺🇸Lee's Summit, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
St. Vincent's Hospital
🇦🇺Darlinghurst, Australia
Royal Brisbane Hospital
🇦🇺Herston, Australia
Peter Lougheed Centre
🇨🇦Calgary, Alberta, Canada
St. Francis Cancer Center
🇺🇸Indianapolis, Indiana, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Duke University Health System
🇺🇸Durham, North Carolina, United States
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
University of California Medical Center
🇺🇸San Francisco, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Jewish Hospital
🇺🇸Cincinnati, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Abramson Cancer Center, University of Pennsylvania Health System
🇺🇸Philadelphia, Pennsylvania, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
University of Pittsburgh Cancer Centers
🇺🇸Pittsburgh, Pennsylvania, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
University of Alabama Birmingham (UAB) Hospital
🇺🇸Birmingham, Alabama, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Tufts New England Medical Center
🇺🇸Boston, Massachusetts, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Mayo Medical Center
🇺🇸Rochester, Minnesota, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Wake Forest University School of Medicine
🇺🇸Winston-Salem, North Carolina, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Medical University of South Carolina(MUSC)
🇺🇸Charleston, South Carolina, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of North Carolina Hospitals
🇺🇸Chapel Hill, North Carolina, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States