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

Graft Versus Host Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00366145
• Other study ID #: 280
• Status: Completed
• Phase: Phase 3
• Start date: August 17, 2006
• Est. completion date: May 28, 2009

Study information

• Verified date: February 2022
• Source: Mesoblast, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00476840

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: May 28, 2009
• Est. primary completion date: December 26, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Biological:
• Prochymal®
2 infusions of 2 million cells/kg per week for 4 weeks

Drug:
• Placebo
2 infusions per week for 4 weeks
• Standard of Care for GVHD
Institutionally defined standard of care (e.g., maintenance of steroid treatment and the addition of a second-line therapy)

Locations

Country	Name	City	State
Australia	Royal Brisbane Hospital	Herston	Queensland
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Canada	Co-Medica Research Network	Calgary	Alberta
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	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Hopital du Saint-Sacrement	Quebec
Canada	Hopital Enfant-Jesus	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	British Columbia's Children's Hospital	Vancouver	British Columbia
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Italy	IRCCS Policlinico San Matteo	Pavia
Italy	Universia degli Studi di Pesaro	Pesaro	PU
Switzerland	Kantonsspital Basel	Basel
United Kingdom	Bristol Royal Hospital for Children	Bristol	UK
United Kingdom	Glasgow Royal Infirmary	Glasgow	UK
United Kingdom	John Radcliffe Hospital	Headington	Oxford
United Kingdom	Leeds General Infirmary	Leeds	UK
United Kingdom	Barts & London School of Medicine	London	England
United States	Emory University	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	University of Maryland/Greenbaum	Baltimore	Maryland
United States	Indiana Blood and Bone Marrow Transplant Center	Beech Grove	Indiana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Tufts-New England Medical Center	Boston	Massachusetts
United States	Roswell Park	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
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	Baylor University	Dallas	Texas
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Univeristy of Texas Southwestern Medical Center	Dallas	Texas
United States	Karmanos/Wayne State University	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke University	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	Univeristy of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Univeristy of Mississippi Medical Center	Jackson	Mississippi
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Louisville	Louisville	Kentucky
United States	University of Wisconsin Madison	Madison	Wisconsin
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Columbia University/New York Presbyterian Hospital	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York Presbyterian Hospital	New York	New York
United States	University of Nebraska	Omaha	Nebraska
United States	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth/Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Texas Research Center	San Antonio	Texas
United States	Univeristy of California San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Louisiana State University	Shreveport	Louisiana
United States	Arizona Cancer Center	Tucson	Arizona
United States	New York Medical College	Valhalla	New York
United States	Wake Forest Univeristy School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Mesoblast, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Italy,  Switzerland,  United Kingdom, 

References & Publications (5)

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. — View Citation

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

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. — View Citation

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

Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival at 180 days Post First Infusion	Percentage of participants who survived at 180 days post first infusion.	Day 180

External 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