Efficacy and Safety of Prochymal™ Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute GVHD

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mesoblast, Ltd.
ClinicalTrials.gov Identifier:
NCT00562497
First received: November 20, 2007
Last updated: April 15, 2014
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Graft Versus Host Disease
Drug: Prochymal
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mesoblast, Ltd.:

Primary Outcome Measures:
  • Achieved an induction of a complete response, Followed by 28 days of maintenance of a clinically meaningful response that does not did not require an increase in corticosteroid dose , did not require second line therapy and survived 90 days. [ Time Frame: 90 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response, Induction of a two grade decrease in GVHD and Maintenance, Induction of a CR lasting ≥14 days, Time to CR, Incidence of CR per organ, Total steroid dose through Day 90, Incidence of Steroid/Infectious complications [ Time Frame: 90 Days ] [ Designated as safety issue: No ]

Enrollment: 184
Study Start Date: September 2007
Study Completion Date: May 2010
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2
Placebo
Other: Placebo
Subjects will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Subjects assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all subjects 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.
Active Comparator: 1
Subjects assigned to the active treatment group will receive Prochymal™.
Drug: Prochymal
Subjects will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Subjects assigned to the active treatment group will receive Prochymal™ at 2 x 106 hMSC/kg per infusion.

Detailed Description:

Subjects will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Subjects assigned to the active treatment group will receive Prochymal™. Subjects assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all subjects 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.

Subjects 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 subject enrollment. Subjects will be followed for safety for 12 months post 1st infusion (Day 0).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be 18 years to 70 years of age, inclusive
  • Subjects 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.
  • Subjects 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.
  • Subjects 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.
  • Subjects must have adequate renal function as defined by: Calculated Creatinine Clearance of >30mL/min using the Cockroft-Gault equation
  • Subjects who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male subjects must use adequate contraception
  • Subject must have a minimum Karnofsky Performance Level of at least 30 at the time of study entry
  • Subject (or legal representative where appropriate) must be capable of providing written informed consent.

Exclusion Criteria:

  • Subject has been previously treated with systemic immunosuppressive therapy for acute GVHD
  • Subject has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the subject including uncontrolled infection, heart failure, pulmonary hypertension, etc.
  • Subjects 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.
  • Subject has a known allergy to bovine or porcine products or DMSO
  • Subject has received a transplant for a solid tumor disease.
  • Subject requires more than 2L/min of oxygen to maintain stable SaO2 greater than or equal to 92%
  • Subject 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00562497

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Birmingham (UAB) Hospital
Birmingham, Alabama, United States, 35249
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
University of California Medical Center
San Francisco, California, United States, 94143
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Florida
University of Florida
Gainsville, Florida, United States, 32610
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Illinois
University of Chicago Hospitals
Chicago, Illinois, United States, 60637
Rush University Medical Center
Chicago, Illinois, United States, 60612
Northwestern Center for Clinical Research
Chicago, Illinois, United States, 60611
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
St. Francis Cancer Center
Indianapolis, Indiana, United States, 46237
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Tufts New England Medical Center
Boston, Massachusetts, United States, 02111
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Medical Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
Kansas City Cancer Center
Lee's Summit, Missouri, United States, 64064
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
New York Presbyterian Hospital
New York, New York, United States, 10065
Mount Sinai School of Medicine
New York, New York, United States, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
University of North Carolina Hospitals
Chapel Hill, North Carolina, United States, 27514
Duke University Health System
Durham, North Carolina, United States, 27705
Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Jewish Hospital
Cincinnati, Ohio, United States, 45236
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Abramson Cancer Center, University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
University of Pittsburgh Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
Oncology Hematology Association
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Medical University of South Carolina(MUSC)
Charleston, South Carolina, United States, 29425
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6001
Australia
St. Vincent's Hospital
Darlinghurst, Australia, NSW 2010
Royal Brisbane Hospital
Herston, Australia, QLD 4029
Canada, Alberta
Peter Lougheed Centre
Calgary, Alberta, Canada, T1Y 6J4
Canada, Ontario
Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Mesoblast, Ltd.
Investigators
Study Director: Rod L Monroy, Ph.D. Osiris Therapeutics, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Mesoblast, Ltd.
ClinicalTrials.gov Identifier: NCT00562497     History of Changes
Other Study ID Numbers: 265
Study First Received: November 20, 2007
Last Updated: April 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mesoblast, Ltd.:
Acute GVHD
Acute Graft Versus Host Disease

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014