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

NCT00562497 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 265
• Study Type: interventional
• Target: 192
• Locations: 3 countries
• Sites: 53

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.

Conditions

Graft Versus Host Disease

Keywords

Acute GVHD; Acute Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Percentage of Participants with Overall Response

  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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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; Other: Corticosteroid

Prochymal® 2x10^6 hMSC/kg

ACTIVE COMPARATOR

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.

Drug: Prochymal®; Other: Corticosteroid

Interventions

Prochymal® DRUG

Prochymal® intravenous infusion.

Also known as: Remestemcel-L

Prochymal® 2x10^6 hMSC/kg

Placebo OTHER

Placebo-matching Prochymal® intravenous infusion.

Placebo

Corticosteroid OTHER

Administration will be intravenously as prescribed by the caregiver.

Also known as: Methylprednisolone, Prednisone

Placebo; Prochymal® 2x10^6 hMSC/kg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mesoblast, Inc.: lead

Study Sites (53)

University of Alabama Birmingham (UAB) Hospital

Birmingham, Alabama, 35249, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of California Medical Center

San Francisco, California, 94143, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern Center for Clinical Research

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Hospitals

Chicago, Illinois, 60637, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

St. Francis Cancer Center

Indianapolis, Indiana, 46237, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tufts New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Medical Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Kansas City Cancer Center

Lee's Summit, Missouri, 64064, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

New York Presbyterian Hospital

New York, New York, 10065, United States

Location

University of North Carolina Hospitals

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Health System

Durham, North Carolina, 27705, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Jewish Hospital

Cincinnati, Ohio, 45236, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Abramson Cancer Center, University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Oncology Hematology Association

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Pittsburgh Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical University of South Carolina(MUSC)

Charleston, South Carolina, 29425, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6001, Australia

Location

St. Vincent's Hospital

Darlinghurst, NSW 2010, Australia

Location

Royal Brisbane Hospital

Herston, QLD 4029, Australia

Location

Peter Lougheed Centre

Calgary, Alberta, T1Y 6J4, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related 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

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

remestemcel-l; Adrenal Cortex Hormones; Methylprednisolone; Prednisone

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Study Officials

• Christopher James, PA

  Mesoblast, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2007
• First Posted: November 22, 2007
• Study Start: January 31, 2008
• Primary Completion: July 14, 2009
• Study Completion: May 20, 2010
• Last Updated: January 19, 2022

Record last verified: 2022-01

Locations

AU (5); CA (3); US (45)