Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease (GVHD)
- Conditions
- Graft Versus Host Disease
- Interventions
- Biological: Prochymal®Drug: PlaceboDrug: Standard of Care for GVHD
- Registration Number
- NCT00366145
- Lead Sponsor
- Mesoblast, Inc.
- Brief Summary
The purpose of this study is to evaluate the efficacy and gather additional safety information for Prochymal® in participants who have failed to respond to steroid treatment of Grades B-D acute GVHD.
- Detailed Description
Approximately 6300 patients receive allogeneic hematopoietic stem cell transplants in the United States each year (International Bone Marrow Transplant Registry \[IBMTR\], 2003). Nearly 50% (approximately 3,150) of these patients develop acute GVHD (Goker et al). A fraction of these patients (approximately 870) will progress to the severe stages of the disease, Grades III-IV. It is estimated that nearly 82% of those patients with severe acute GVHD will be steroid refractory (Przepiorka et al., 1995) and of these, only 50% of steroid-refractory patients will respond to secondary and tertiary treatments (Greinix et al., 2000). Thus, roughly 350 patients each year face tremendous odds against survival. In addition, most patients who initially responded to secondary and tertiary treatments have a high risk of dying within the first year (Remberger et al., 2001; Anasetti et al., 1994). Development of new therapeutic agents and strategies to rescue patients with steroid refractory, acute GVHD would provide a significant benefit in an area of unmet medical need. Participants will receive standard of care in addition to adult mesenchymal stem cells or placebo.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 260
- Participant must be 6 months to 70 years of age, inclusive.
- Participants who have failed to respond to steroid treatment.
Failure to respond to steroid treatment is defined as any grade B-D (IBMTR) grading of acute GVHD that shows:
- No improvement after 3 days and a duration of no greater than 2 weeks while receiving treatment with methylprednisolone (greater than or equal to 1 mg/kg/day) or equivalent.
- Participant must be treated within 4 days of randomization. In urgent situations 2nd line therapy may be started 24 hours prior to randomization, and Prochymal® must be initiated within the following 3 days.
- Participants who have received an increase in their steroid dose treatment prior to randomization will be eligible for enrollment. An increase in steroid dose will not be considered as second line therapy.
- Participant must have adequate renal function as defined by: Calculated Creatinine Clearance of >30 milliliters per minute (mL/min) using the Cockcroft-Gault equation.
- For pediatric participants: Schwartz equation: (Participant population: infants over 1 week old through adolescence (<18 years old).
- 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 started treatment with second line therapy >24 hours prior to randomization.
- Participant has received agents other than steroids for primary treatment of acute GVHD.
- Participant is participating in the CTN Protocol 0302.
- 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.
- Participant may not receive any other investigational agents (not approved by the FDA) concurrently during study participation or within 30 days of randomization.
- Participant has a known allergy to bovine or porcine products.
- Participant has received a transplant for a solid tumor disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prochymal® Prochymal® Participants who receive standard of care plus treatment with ex vivo cultured adult human mesenchymal stem cells. Placebo Placebo Participants who receive standard of care and do not receive treatment with ex vivo cultured adult human mesenchymal stem cells. Prochymal® Standard of Care for GVHD Participants who receive standard of care plus treatment with ex vivo cultured adult human mesenchymal stem cells. Placebo Standard of Care for GVHD Participants who receive standard of care and do not receive treatment with ex vivo cultured adult human mesenchymal stem cells.
- Primary Outcome Measures
Name Time Method Percentage of Participants achieving Complete Response of Greater Than or Equal to 28 Days Duration up to 100 Days post first infusion A complete response was defined as complete resolution of all clinical signs of Graft versus host disease (GVHD)- that had to be maintained for at least 28 consecutive days (durable complete response \[DCR\]) within 100 days post first infusion.
- Secondary Outcome Measures
Name Time Method Overall Survival at 180 days Post First Infusion Day 180 Percentage of participants who survived at 180 days post first infusion.
Trial Locations
- Locations (70)
Emory University
🇺🇸Atlanta, Georgia, United States
University of Maryland/Greenbaum
🇺🇸Baltimore, Maryland, United States
Baylor University
🇺🇸Dallas, Texas, United States
Univeristy of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Royal Brisbane Hospital
🇦🇺Herston, Queensland, Australia
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
University of Illinois - Chicago
🇺🇸Chicago, Illinois, United States
Tufts-New England Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of Miami
🇺🇸Miami, Florida, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Roswell Park
🇺🇸Buffalo, New York, United States
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
University of Rochester
🇺🇸Rochester, New York, United States
New York Medical College
🇺🇸Valhalla, New York, United States
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Cancer Care Manitoba
🇨🇦Winnipeg, Manitoba, Canada
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
City of Hope
🇺🇸Duarte, California, United States
Univeristy of California San Francisco
🇺🇸San Francisco, California, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Northwestern Center for Clinical Research
🇺🇸Chicago, Illinois, United States
Univeristy of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Indiana Blood and Bone Marrow Transplant Center
🇺🇸Beech Grove, Indiana, United States
Louisiana State University
🇺🇸Shreveport, Louisiana, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Karmanos/Wayne State University
🇺🇸Detroit, Michigan, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Columbia University/New York Presbyterian Hospital
🇺🇸New York, New York, United States
Wake Forest Univeristy School of Medicine
🇺🇸Winston-Salem, North Carolina, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Western Pennsylvania Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Cancer Center at Medical City
🇺🇸Dallas, Texas, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Texas Research Center
🇺🇸San Antonio, Texas, United States
Virginia Commonwealth/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
University of Wisconsin Madison
🇺🇸Madison, Wisconsin, United States
British Columbia's Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Co-Medica Research Network
🇨🇦Calgary, Alberta, Canada
London Health Sciences Centre- Westminster Campus
🇨🇦London, Ontario, Canada
Hamilton Health Sciences Centre
🇨🇦Hamilton, Ontario, Canada
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Maisonneuve-Rosemont Hospital
🇨🇦Montreal, Quebec, Canada
Hopital Enfant-Jesus
🇨🇦Quebec, Canada
Hopital du Saint-Sacrement
🇨🇦Quebec, Canada
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Universia degli Studi di Pesaro
🇮🇹Pesaro, PU, Italy
Kantonsspital Basel
🇨🇭Basel, Switzerland
John Radcliffe Hospital
🇬🇧Headington, Oxford, United Kingdom
Bristol Royal Hospital for Children
🇬🇧Bristol, UK, United Kingdom
Barts & London School of Medicine
🇬🇧London, England, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, UK, United Kingdom
Glasgow Royal Infirmary
🇬🇧Glasgow, UK, United Kingdom
University of Louisville
🇺🇸Louisville, Kentucky, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Univeristy of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Duke University
🇺🇸Durham, North Carolina, United States
University of Nebraska
🇺🇸Omaha, Nebraska, United States
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States