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

NCT ID: NCT00366145

Last Updated: 2022-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-17
• Study Completion Date: 2009-05-28

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.

Detailed Description

Approximately 6300 patients receive allogeneic hematopoietic stem cell transplants in the United States each year (International Bone Marrow Transplant Registry [IBMTR], 2003). Nearly 50% (approximately 3,150) of these patients develop acute GVHD (Goker et al). A fraction of these patients (approximately 870) will progress to the severe stages of the disease, Grades III-IV. It is estimated that nearly 82% of those patients with severe acute GVHD will be steroid refractory (Przepiorka et al., 1995) and of these, only 50% of steroid-refractory patients will respond to secondary and tertiary treatments (Greinix et al., 2000). Thus, roughly 350 patients each year face tremendous odds against survival. In addition, most patients who initially responded to secondary and tertiary treatments have a high risk of dying within the first year (Remberger et al., 2001; Anasetti et al., 1994). Development of new therapeutic agents and strategies to rescue patients with steroid refractory, acute GVHD would provide a significant benefit in an area of unmet medical need. Participants will receive standard of care in addition to adult mesenchymal stem cells or placebo.

Conditions

Graft Versus Host Disease

Study Design

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

Study Groups

Prochymal®

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

Group Type: ACTIVE_COMPARATOR

Prochymal®

Intervention Type: BIOLOGICAL

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

Standard of Care for GVHD

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

2 infusions per week for 4 weeks

Standard of Care for GVHD

Intervention Type: DRUG

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

Interventions

Prochymal®

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

Intervention Type: BIOLOGICAL

Placebo

2 infusions per week for 4 weeks

Intervention Type: DRUG

Standard of Care for GVHD

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

Intervention Type: DRUG

Other Intervention Names

Mesenchymal Stem Cells; excipients without adult human mesenchymal stem cells

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 6 Months
• 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 at Birmingham

Birmingham, Alabama, United States

Arizona Cancer Center

Tucson, Arizona, United States

City of Hope

Duarte, California, United States

Univeristy of California San Francisco

San Francisco, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

University of Miami

Miami, Florida, United States

All Children's Hospital

St. Petersburg, 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 Illinois - Chicago

Chicago, Illinois, United States

Indiana Blood and Bone Marrow Transplant Center

Beech Grove, Indiana, United States

Univeristy of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Louisville

Louisville, Kentucky, United States

Louisiana State University

Shreveport, Louisiana, United States

University of Maryland/Greenbaum

Baltimore, Maryland, United States

Tufts-New England Medical Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos/Wayne State University

Detroit, Michigan, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Univeristy of Mississippi Medical Center

Jackson, Mississippi, United States

University of Nebraska

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park

Buffalo, New York, United States

New York Presbyterian Hospital

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University/New York Presbyterian Hospital

New York, New York, United States

University of Rochester

Rochester, New York, United States

New York Medical College

Valhalla, New York, United States

Duke University

Durham, North Carolina, United States

Wake Forest Univeristy School of Medicine

Winston-Salem, North Carolina, United States

Oregon Health and Science University

Portland, Oregon, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Western Pennsylvania Cancer Institute

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Texas Cancer Center at Medical City

Dallas, Texas, United States

Baylor University

Dallas, Texas, United States

Univeristy of Texas Southwestern Medical Center

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Texas Research Center

San Antonio, Texas, United States

Virginia Commonwealth/Massey Cancer Center

Richmond, Virginia, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

University of Wisconsin Madison

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Royal Brisbane Hospital

Herston, Queensland, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Co-Medica Research Network

Calgary, Alberta, Canada

British Columbia's Children's Hospital

Vancouver, British Columbia, Canada

Cancer Care Manitoba

Winnipeg, Manitoba, Canada

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Hamilton Health Sciences Centre

Hamilton, Ontario, Canada

London Health Sciences Centre- Westminster Campus

London, Ontario, Canada

Ottawa Hospital

Ottawa, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Hopital Enfant-Jesus

Québec, , Canada

Hopital du Saint-Sacrement

Québec, , Canada

Universia degli Studi di Pesaro

Pesaro, PU, Italy

IRCCS Policlinico San Matteo

Pavia, , Italy

Kantonsspital Basel

Basel, , Switzerland

Barts & London School of Medicine

London, England, United Kingdom

John Radcliffe Hospital

Headington, Oxford, United Kingdom

Bristol Royal Hospital for Children

Bristol, UK, United Kingdom

Glasgow Royal Infirmary

Glasgow, UK, United Kingdom

Leeds General Infirmary

Leeds, UK, United Kingdom

Countries

United States; Australia; Canada; Italy; Switzerland; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 11823036 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10989188 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15846293 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15121408 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 16040382 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27515308 (View on PubMed)

Related Links

http://www.osiris.com

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

Other Identifiers

280

Identifier Type: -

Identifier Source: org_study_id

NCT00476840

Identifier Type: -

Identifier Source: nct_alias