Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Patients Who Have Failed to Respond to Steroid Treatment for Acute Graft Versus Host Disease (GVHD)

Condition(s) targeted: Graft Versus Host Disease

Intervention: Mesenchymal Stem Cells (Biological); placebo (Biological)

Phase: Phase 3

Status: Recruiting

Sponsored by: Osiris Therapeutics

Official(s) and/or principal investigator(s):
Paul Martin, MD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Center

Overall contact:
Moya Daniels, B.S., Phone: 443-545-1805, Email: mmdaniels@osiris.com

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

Official title: A Phase III, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal(Ex Vivo Cultured Adult Human Mesenchymal Stem Cells) Infusion for the Treatment of Patients Who Have Failed to Respond to Steroid Treatment for Acute GVHD

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Complete Response of greater than or equal to 28 days duration

Secondary outcome: Survival at 180 days post first infusion

Detailed description: Approximately 6300 patients receive allogeneic hematopoietic stem cell transplants in the United States each year (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 wll 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.

Patients will receive standard of care in addition to adult mesenchymal stem cells or placebo.

Minimum age: 6 Months. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subjects must be 6 months to 70 years of age, inclusive

- Subjects 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.

- Subjects 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.

- Subjects 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.

- Subjects must have adequate renal function as defined by: Calculated Creatinine

Clearance of >30mL/min using the Cockroft Gault equation

- For pediatric patients: Schwartz equation: (Patient population: infants over 1 week

old through adolescence (<18 years old)

- Subjects who are women of childbearing potential, must be non-pregnant, not

breast-feeding, and use adequate contraception. Male subjects must use adequate contraception

- Subject must have a minimum Karnofsky Performance Level of at least 30 at the time of

study entry

- Subject (or legal representative where appropriate) must be capable of providing

written informed consent.

Exclusion Criteria:

- Subject has started treatment with second line therapy >24 hours prior to

randomization.

- Subject has received agents other than steroids for primary treatment of acute GVHD

- Subject is participating in the CTN Protocol 0302

- Subject has any underlying or current medical or psychiatric condition that, in the

opinion of the Investigator, would interfere with the evaluation of the subject including uncontrolled infection, heart failure, pulmonary hypertension, etc.

- Subjects may not receive any other investigational agents (not approved by the FDA)

concurrently during study participation or within 30 days of randomization.

- Subject has a known allergy to bovine or porcine products.

- Subject has received a transplant for a solid tumor disease.

Moya Daniels, B.S., Phone: 443-545-1805, Email: mmdaniels@osiris.com

Hopital du Saint-Sacrement, Quebec G1S4L8, Canada; Recruiting

Hopital Enfant-Jesus, Quebec G1J 1Z4, Canada; Recruiting

IRCCS Policlinico San Matteo, Pavia 27100, Italy; Recruiting

Kantonsspital Basel, Basel 4031, Switzerland; Recruiting

University of Alabama at Birmingham, Birmingham, Alabama 35249, United States; Recruiting

Co-Medica Research Network, Calgary, Alberta T1Y6J4, Canada; Recruiting

Arizona Cancer Center, Tucson, Arizona 85724, United States; Recruiting

British Columbia's Children's Hospital, Vancouver, British Columbia V6H3V4, Canada; Recruiting

City of Hope, Duarte, California 91010, United States; Recruiting

Univeristy of California San Francisco, San Francisco, California 94143, United States; Recruiting

Yale New Haven Hospital, New Haven, Connecticut 06520, United States; Withdrawn

Barts & London School of Medicine, London, England EC1M 6BQ, United Kingdom; Recruiting

University of Miami, Miami, Florida 33136, United States; Recruiting

All Children's Hospital, St. Petersburg, Florida 33701, United States; Recruiting

Northside Hospital, Atlanta, Georgia 30342, United States; Recruiting

Emory University, Atlanta, Georgia 30322, United States; Recruiting

Rush University Medical Center, Chicago, Illinois 60612, United States; Recruiting

Northwestern Center for Clinical Research, Chicago, Illinois 60611, United States; Recruiting

University of Illinois - Chicago, Chicago, Illinois 60612, United States; Recruiting

Indiana Blood and Bone Marrow Transplant Center, Beech Grove, Indiana 46107, United States; Recruiting

Univeristy of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United States; Recruiting

University of Kansas Medical Center, Kansas City, Kansas 66160, United States; Recruiting

University of Louisville, Louisville, Kentucky 40202, United States; Recruiting

Louisiana State University, Shreveport, Louisiana 71130, United States; Withdrawn

Cancer Care Manitoba, Winnipeg, Manitoba R3E0V9, Canada; Recruiting

University of Maryland/Greenbaum, Baltimore, Maryland 21201, United States; Recruiting

Tufts-New England Medical Center, Boston, Massachusetts 02111, United States; Recruiting

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Recruiting

Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States; Recruiting

Karmanos/Wayne State University, Detroit, Michigan 48201, United States; Recruiting

Mayo Clinic Rochester, Rochester, Minnesota 55905, United States; Recruiting

Univeristy of Mississippi Medical Center, Jackson, Mississippi 39216, United States; Recruiting

University of Nebraska, Omaha, Nebraska 68198, United States; Recruiting

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States; Recruiting

Mount Sinai Medical Center, New York, New York 10029, United States; Recruiting

New York Medical College, Valhalla, New York 10595, United States; Recruiting

Roswell Park, Buffalo, New York 14263, United States; Recruiting

New York Presbyterian Hospital, New York, New York 10021, United States; Recruiting

University of Rochester, Rochester, New York 14642, United States; Recruiting

Columbia University/New York Presbyterian Hospital, New York, New York 10032, United States; Recruiting

Duke University, Durham, North Carolina 27710, United States; Recruiting

Wake Forest Univeristy School of Medicine, Winston Salem, North Carolina 27157, United States; Recruiting

Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H2Y9, Canada; Recruiting

Toronto General Hospital, Toronto, Ontario M5G 1X8, Canada; Recruiting

Ottawa Hospital, Ottawa, Ontario K1H8L6, Canada; Recruiting

Princess Margaret Hospital, Toronto, Ontario M5G1X8, Canada; Recruiting

Hamilton Health Sciences Centre, Hamilton, Ontario L8N3Z5, Canada; Recruiting

London Health Sciences Centre- Westminster Campus, London, Ontario N6A4G5, Canada; Recruiting

Oregon Health and Science University, Portland, Oregon 97239, United States; Recruiting

John Radcliffe Hospital, Headington, Oxford OX3 0Du, United Kingdom; Recruiting

Universia degli Studi di Pesaro, Pesaro, PU 61100, Italy; Recruiting

Western Pennsylvania Cancer Institute, Pittsburgh, Pennsylvania 15224, United States; Recruiting

Penn State Hershey Medical Center, Hershey, Pennsylvania 17033, United States; Recruiting

Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; Recruiting

Royal Brisbane Hospital, Herston, Queensland 4029, Australia; Recruiting

Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting

Texas Cancer Center at Medical City, Dallas, Texas 75230, United States; Recruiting

Baylor University, Dallas, Texas 75246, United States; Recruiting

Texas Research Center, San Antonio, Texas 78229, United States; Recruiting

MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting

Univeristy of Texas Southwestern Medical Center, Dallas, Texas 75390, United States; Recruiting

Glasgow Royal Infirmary, Glasgow, UK G4 OSF, United Kingdom; Recruiting

Bristol Royal Hospital for Children, Bristol, UK BS2 8BJ, United Kingdom; Recruiting

Leeds General Infirmary, Leeds, UK LS1 3EX, United Kingdom; Recruiting

Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; Recruiting

Virginia Commonwealth/Massey Cancer Center, Richmond, Virginia 23298, United States; Recruiting

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States; Recruiting

Royal Perth Hospital, Perth, Western Australia 6100, Australia; Recruiting

University of Wisconsin Madison, Madison, Wisconsin 53792, United States; Recruiting

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States; Recruiting

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

Related publications:

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.

Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000 Aug;28(8):875-84. Review.

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.

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.

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

Starting date: July 2006
Ending date: December 2008
Last updated: June 18, 2008