Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease (GVHD)

NCT00366145 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 280
• Study Type: interventional
• Target: 260
• Locations: 6 countries
• Sites: 70

Brief Summary

The purpose of this study is to evaluate the efficacy and gather additional safety information for Prochymal® in participants who have failed to respond to steroid treatment of Grades B-D acute GVHD.

Conditions

Graft Versus Host Disease

Keywords

Acute GVHD; Steroid refractory GVHD; Severe steroid refractory acute GVHD; Steroid refractory; Steroid Refractory Acute Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants achieving Complete Response of Greater Than or Equal to 28 Days Duration

  A complete response was defined as complete resolution of all clinical signs of Graft versus host disease (GVHD)- that had to be maintained for at least 28 consecutive days (durable complete response \[DCR\]) within 100 days post first infusion.

  up to 100 Days post first infusion

Secondary Outcomes (1)

• Overall Survival at 180 days Post First Infusion

  Day 180

Study Arms (2)

Prochymal®

ACTIVE COMPARATOR

Participants who receive standard of care plus treatment with ex vivo cultured adult human mesenchymal stem cells.

Biological: Prochymal®; Drug: Standard of Care for GVHD

Placebo

PLACEBO COMPARATOR

Participants who receive standard of care and do not receive treatment with ex vivo cultured adult human mesenchymal stem cells.

Drug: Placebo; Drug: Standard of Care for GVHD

Interventions

Prochymal® BIOLOGICAL

2 infusions of 2 million cells/kg per week for 4 weeks

Also known as: Mesenchymal Stem Cells

Prochymal®

Placebo DRUG

2 infusions per week for 4 weeks

Also known as: excipients without adult human mesenchymal stem cells

Placebo

Standard of Care for GVHD DRUG

Institutionally defined standard of care (e.g., maintenance of steroid treatment and the addition of a second-line therapy)

Placebo; Prochymal®

Eligibility Criteria

• Age: 6 Months - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 6 months to 70 years of age, inclusive.
• Participants who have failed to respond to steroid treatment.
• Failure to respond to steroid treatment is defined as any grade B-D (IBMTR) grading of acute GVHD that shows:
• No improvement after 3 days and a duration of no greater than 2 weeks while receiving treatment with methylprednisolone (greater than or equal to 1 mg/kg/day) or equivalent.
• Participant must be treated within 4 days of randomization. In urgent situations 2nd line therapy may be started 24 hours prior to randomization, and Prochymal® must be initiated within the following 3 days.
• Participants who have received an increase in their steroid dose treatment prior to randomization will be eligible for enrollment. An increase in steroid dose will not be considered as second line therapy.
• Participant must have adequate renal function as defined by: Calculated Creatinine Clearance of \>30 milliliters per minute (mL/min) using the Cockcroft-Gault equation.
• For pediatric participants: Schwartz equation: (Participant population: infants over 1 week old through adolescence (\<18 years old).
• 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 started treatment with second line therapy \>24 hours prior to randomization.
• Participant has received agents other than steroids for primary treatment of acute GVHD.
• Participant is participating in the CTN Protocol 0302.
• 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.
• Participant may not receive any other investigational agents (not approved by the FDA) concurrently during study participation or within 30 days of randomization.
• Participant has a known allergy to bovine or porcine products.
• Participant has received a transplant for a solid tumor disease.

Sponsors & Collaborators

• Mesoblast, Inc.: lead

Study Sites (70)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Univeristy of California San Francisco

San Francisco, California, 94143, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, 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 Illinois - Chicago

Chicago, Illinois, 60612, United States

Location

Indiana Blood and Bone Marrow Transplant Center

Beech Grove, Indiana, 46107, United States

Location

Univeristy of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Louisiana State University

Shreveport, Louisiana, 71130, United States

Location

University of Maryland/Greenbaum

Baltimore, Maryland, 21201, United States

Location

Tufts-New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos/Wayne State University

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Univeristy of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park

Buffalo, New York, 14263, United States

Location

New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University/New York Presbyterian Hospital

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Wake Forest Univeristy School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Western Pennsylvania Cancer Institute

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Cancer Center at Medical City

Dallas, Texas, 75230, United States

Location

Baylor University

Dallas, Texas, 75246, United States

Location

Univeristy of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Research Center

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

University of Wisconsin Madison

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal Brisbane Hospital

Herston, Queensland, 4029, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6100, Australia

Location

Co-Medica Research Network

Calgary, Alberta, T1Y6J4, Canada

Location

British Columbia's Children's Hospital

Vancouver, British Columbia, V6H3V4, Canada

Location

Cancer Care Manitoba

Winnipeg, Manitoba, R3E0V9, Canada

Location

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H2Y9, Canada

Location

Hamilton Health Sciences Centre

Hamilton, Ontario, L8N3Z5, Canada

Location

London Health Sciences Centre- Westminster Campus

London, Ontario, N6A4G5, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H8L6, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 1X8, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G1X8, Canada

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Hopital Enfant-Jesus

Québec, G1J 1Z4, Canada

Location

Hopital du Saint-Sacrement

Québec, G1S4L8, Canada

Location

Universia degli Studi di Pesaro

Pesaro, PU, 61100, Italy

Location

IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Kantonsspital Basel

Basel, 4031, Switzerland

Location

Barts & London School of Medicine

London, England, EC1M 6BQ, United Kingdom

Location

John Radcliffe Hospital

Headington, Oxford, OX3 0Du, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, UK, BS2 8BJ, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, UK, G4 OSF, United Kingdom

Location

Leeds General Infirmary

Leeds, UK, LS1 3EX, United Kingdom

Location

Related Publications (6)

• Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002 Jan;30(1):42-8. doi: 10.1016/s0301-472x(01)00769-x.

  PMID: 11823036 BACKGROUND

• Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000 Aug;28(8):875-84. doi: 10.1016/s0301-472x(00)00482-3.

  PMID: 10989188 BACKGROUND

• Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, McCarthy P, Atkinson K, Cooper BW, Gerson SL, Laughlin MJ, Loberiza FR Jr, Moseley AB, Bacigalupo A. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005 May;11(5):389-98. doi: 10.1016/j.bbmt.2005.02.001.

  PMID: 15846293 BACKGROUND

• Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. doi: 10.1016/S0140-6736(04)16104-7.

  PMID: 15121408 BACKGROUND

• Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45. doi: 10.1080/14653240510018118.

  PMID: 16040382 BACKGROUND

• Camilleri ET, Gustafson MP, Dudakovic A, Riester SM, Garces CG, Paradise CR, Takai H, Karperien M, Cool S, Sampen HJ, Larson AN, Qu W, Smith J, Dietz AB, van Wijnen AJ. Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production. Stem Cell Res Ther. 2016 Aug 11;7(1):107. doi: 10.1186/s13287-016-0370-8.

  PMID: 27515308 DERIVED

Related Links

• Description Click here for more information about this study: A Phase III Study to Evaluate the Efficacy and Safety of Prochymal® (Ex vivo Cultured Adult Human Mesenchymal Stem Cells) Infusion for the Treatment of Steroid-Refractory Acute GVHD

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

remestemcel-l; Excipients; Standard of Care

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Vehicles; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Christopher James, PA

  Mesoblast, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 17, 2006
• First Posted: August 21, 2006
• Study Start: August 17, 2006
• Primary Completion: December 26, 2008
• Study Completion: May 28, 2009
• Last Updated: February 10, 2022

Record last verified: 2022-02

Locations

CH (1); GB (5); CA (12); IT (2); AU (3); US (47)