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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Graft Versus Host Disease	Biological: Mesenchymal Stem Cells; Biological: placebo	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	240 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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 Steroid Refractory Acute GVHD
Study Start Date :	July 2006
Actual Primary Completion Date :	May 2009
Actual Study Completion Date :	May 2009

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: 1; Patients who receive standard of care plus treatment with ex vivo cultured adult human Mesenchymal Stem Cells	Biological: Mesenchymal Stem Cells; 2 million cells/kg twice a week for 4 weeks; Other Name: Prochymal
Placebo Comparator: 2; Patients who receive standard of care and do not receive treatment with ex vivo cultured adult human mesenchymal stem cells.	Biological: placebo; 2 infusions a week for 4 weeks; Other Name: excipients without adult human mesenchymal stem cells

Outcome Measures

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Primary Outcome Measures :

1. Complete Response of greater than or equal to 28 days duration [ Time Frame: Day 100 ]

Secondary Outcome Measures :

1. Survival at 180 days post first infusion [ Time Frame: 180 Days ]

Eligibility Criteria

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Ages Eligible for Study:	6 Months to 70 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 70 Study Locations

Sponsors and Collaborators

Osiris Therapeutics

Investigators

Principal Investigator:	Paul Martin, MD	Fred Hutchinson Cancer Center

More Information

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Additional Information:

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 

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, 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.

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Osiris Therapeutics
ClinicalTrials.gov Identifier:	NCT00366145 History of Changes
Obsolete Identifiers:	NCT00476840
Other Study ID Numbers:	280
First Posted:	August 21, 2006
Last Update Posted:	October 13, 2011
Last Verified:	October 2011

Keywords provided by Osiris Therapeutics:

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

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases