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

NCT ID: NCT00562497

Last Updated: 2022-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2010-05-20

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).

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo-matching Prochymal® intravenous infusion.

Corticosteroid

Intervention Type: OTHER

Administration will be intravenously as prescribed by the caregiver.

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.

Group Type: ACTIVE_COMPARATOR

Prochymal®

Intervention Type: DRUG

Prochymal® intravenous infusion.

Corticosteroid

Intervention Type: OTHER

Administration will be intravenously as prescribed by the caregiver.

Interventions

Prochymal®

Prochymal® intravenous infusion.

Intervention Type: DRUG

Placebo

Placebo-matching Prochymal® intravenous infusion.

Intervention Type: OTHER

Corticosteroid

Administration will be intravenously as prescribed by the caregiver.

Intervention Type: OTHER

Other Intervention Names

Remestemcel-L; Methylprednisolone; Prednisone

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mesoblast, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher James, PA

Role: STUDY_DIRECTOR

Mesoblast, Inc.

Locations

University of Alabama Birmingham (UAB) Hospital

Birmingham, Alabama, United States

UCLA Medical Center

Los Angeles, California, United States

University of California Medical Center

San Francisco, California, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

University of Florida

Gainesville, Florida, United States

Emory University

Atlanta, Georgia, United States

Northside Hospital

Atlanta, Georgia, United States

Northwestern Center for Clinical Research

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Hospitals

Chicago, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Indiana University Cancer Center

Indianapolis, Indiana, United States

St. Francis Cancer Center

Indianapolis, Indiana, United States

University of Louisville

Louisville, Kentucky, United States

Tufts New England Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Medical Center

Rochester, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Kansas City Cancer Center

Lee's Summit, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

New York Presbyterian Hospital

New York, New York, United States

University of North Carolina Hospitals

Chapel Hill, North Carolina, United States

Duke University Health System

Durham, North Carolina, United States

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 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

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Oncology Hematology Association

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Cancer Centers

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina(MUSC)

Charleston, South Carolina, United States

Baylor University Medical Center

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Texas Transplant Institute

San Antonio, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

St. Vincent's Hospital

Darlinghurst, , Australia

Royal Brisbane Hospital

Herston, , Australia

Peter Lougheed Centre

Calgary, Alberta, Canada

Ottawa Hospital

Ottawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Australia; Canada

Related Links

http://www.osiris.com

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

Other Identifiers

265

Identifier Type: -

Identifier Source: org_study_id