Back to resultsEfficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute Graft Versus Host Disease (GVHD)
Primary Purpose
Graft Versus Host Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Prochymal®
Placebo
Corticosteroid
Sponsored by
About this trial
This is an interventional treatment trial for Graft Versus Host Disease focused on measuring Acute GVHD, Acute Graft Versus Host Disease
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.
Sites / Locations
- University of Alabama Birmingham (UAB) Hospital
- UCLA Medical Center
- University of California Medical Center
- Rocky Mountain Cancer Center
- University of Florida
- Emory University
- Northside Hospital
- Northwestern Center for Clinical Research
- Rush University Medical Center
- University of Chicago Hospitals
- Loyola University Medical Center
- Indiana University Cancer Center
- St. Francis Cancer Center
- University of Louisville
- Tufts New England Medical Center
- Massachusetts General Hospital
- Dana Farber Cancer Institute
- Beth Israel Deaconess Medical Center
- Barbara Ann Karmanos Cancer Institute
- Mayo Medical Center
- University of Mississippi Medical Center
- Kansas City Cancer Center
- Washington University School of Medicine
- Roswell Park Cancer Institute
- Memorial Sloan Kettering Cancer Center
- Mount Sinai School of Medicine
- New York Presbyterian Hospital
- University of North Carolina Hospitals
- Duke University Health System
- Wake Forest University School of Medicine
- Jewish Hospital
- Ohio State University
- Penn State Milton S. Hershey Medical Center
- Abramson Cancer Center, University of Pennsylvania Health System
- Thomas Jefferson University
- Western Pennsylvania Hospital
- Oncology Hematology Association
- University of Pittsburgh Cancer Centers
- Medical University of South Carolina(MUSC)
- Baylor University Medical Center
- MD Anderson Cancer Center
- Texas Transplant Institute
- Virginia Commonwealth University
- Fred Hutchinson Cancer Research Center
- Medical College of Wisconsin
- Royal Adelaide Hospital
- Royal Melbourne Hospital
- Royal Perth Hospital
- St. Vincent's Hospital
- Royal Brisbane Hospital
- Peter Lougheed Centre
- Ottawa Hospital
- Princess Margaret Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
Prochymal® 2x10^6 hMSC/kg
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Percentage of Participants with Overall Response
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
Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days
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
Percentage of Participants with Induction of PR during the first 28 days
Time to achieve CR
Number of CR per organ
Total corticosteroid dose administered
Number of corticosteroid-related complications
Corticosteroid-related complications included hyperglycemia requiring insulin, corticosteroid myopathy and psychosis.
Number of Infectious complications
Infectious complications included viral, fungal or bacterial complications.
Number of Days of Hospitalization
Average Daily Corticosteroid Dose
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00562497
Brief Title
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
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
January 31, 2008 (Actual)
Primary Completion Date
July 14, 2009 (Actual)
Study Completion Date
May 20, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mesoblast, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease
Keywords
Acute GVHD, Acute Graft Versus Host Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
192 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Prochymal® 2x10^6 hMSC/kg
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Prochymal®
Other Intervention Name(s)
Remestemcel-L
Intervention Description
Prochymal® intravenous infusion.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo-matching Prochymal® intravenous infusion.
Intervention Type
Other
Intervention Name(s)
Corticosteroid
Other Intervention Name(s)
Methylprednisolone, Prednisone
Intervention Description
Administration will be intravenously as prescribed by the caregiver.
Primary Outcome Measure Information:
Title
Percentage of Participants with Treatment Success
Description
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.
Time Frame
90 Days
Secondary Outcome Measure Information:
Title
Percentage of Participants with Overall Response
Description
Overall Response was defined as participants who achieved complete response or partial response (CR+PR).
Time Frame
Day 90
Title
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
Time Frame
Up to Day 56
Title
Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days
Time Frame
Day 14
Title
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
Time Frame
Up to Day 56
Title
Percentage of Participants with Induction of PR during the first 28 days
Time Frame
Up to Day 28
Title
Time to achieve CR
Time Frame
Up to Day 90
Title
Number of CR per organ
Time Frame
Up to Day 90
Title
Total corticosteroid dose administered
Time Frame
Up to Day 90
Title
Number of corticosteroid-related complications
Description
Corticosteroid-related complications included hyperglycemia requiring insulin, corticosteroid myopathy and psychosis.
Time Frame
Up to Day 90
Title
Number of Infectious complications
Description
Infectious complications included viral, fungal or bacterial complications.
Time Frame
Up to Day 90
Title
Number of Days of Hospitalization
Time Frame
Up to Day 90
Title
Average Daily Corticosteroid Dose
Time Frame
Up to Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher James, PA
Organizational Affiliation
Mesoblast, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama Birmingham (UAB) Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northside Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Northwestern Center for Clinical Research
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago Hospitals
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
St. Francis Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Tufts New England Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Medical Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Kansas City Cancer Center
City
Lee's Summit
State/Province
Missouri
ZIP/Postal Code
64064
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of North Carolina Hospitals
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Wake Forest University School of Medicine
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Jewish Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Abramson Cancer Center, University of Pennsylvania Health System
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Western Pennsylvania Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Oncology Hematology Association
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
University of Pittsburgh Cancer Centers
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Medical University of South Carolina(MUSC)
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Transplant Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Royal Perth Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6001
Country
Australia
Facility Name
St. Vincent's Hospital
City
Darlinghurst
ZIP/Postal Code
NSW 2010
Country
Australia
Facility Name
Royal Brisbane Hospital
City
Herston
ZIP/Postal Code
QLD 4029
Country
Australia
Facility Name
Peter Lougheed Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T1Y 6J4
Country
Canada
Facility Name
Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
12. IPD Sharing Statement
Links:
URL
http://www.osiris.com
Description
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
Learn more about this trial
Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute Graft Versus Host Disease (GVHD)
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