Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute Graft Versus Host Disease (GVHD)

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

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.

Study Overview

• Status: Completed
• Conditions: Graft Versus Host Disease
• Intervention / Treatment: Other: Placebo; Other: Corticosteroid; Drug: Prochymal®

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).

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Other: Placebo; Placebo-matching Prochymal® intravenous infusion.; Other: Corticosteroid; Administration will be intravenously as prescribed by the caregiver.; Other Names: Methylprednisolone; Prednisone
Active Comparator: Prochymal® 2x10^6 hMSC/kg; 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.	Other: Corticosteroid; Administration will be intravenously as prescribed by the caregiver.; Other Names: Methylprednisolone; Prednisone; Drug: Prochymal®; Prochymal® intravenous infusion.; Other Names: Remestemcel-L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	90 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Overall Response	Overall Response was defined as participants who achieved complete response or partial response (CR+PR).	Day 90
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 CR lasting for greater than or equal to 14 Days		Day 14
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
Percentage of Participants with Induction of PR during the first 28 days		Up to Day 28
Time to achieve CR		Up to Day 90
Number of CR per organ		Up to Day 90
Total corticosteroid dose administered		Up to Day 90
Number of corticosteroid-related complications	Corticosteroid-related complications included hyperglycemia requiring insulin, corticosteroid myopathy and psychosis.	Up to Day 90
Number of Infectious complications	Infectious complications included viral, fungal or bacterial complications.	Up to Day 90
Number of Days of Hospitalization		Up to Day 90
Average Daily Corticosteroid Dose		Up to Day 90

Collaborators and Investigators

• Sponsor: Mesoblast, Inc.

Publications and helpful links

Helpful Links

• 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

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2008
• Primary Completion (Actual): July 14, 2009
• Study Completion (Actual): May 20, 2010

Study Registration Dates

• First Submitted: November 20, 2007
• First Submitted That Met QC Criteria: November 20, 2007
• First Posted (Estimate): November 22, 2007

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Acute Graft Versus Host Disease; Acute GVHD
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Methylprednisolone; Prednisone; Remestemcel-l
• Other Study ID Numbers: 265

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No