Safety and Efficacy Study of Adult Human Mesenchymal Stem Cells to Treat Acute GVHD. - Full Text View

Sponsor:	Osiris Therapeutics
Information provided by:	Osiris Therapeutics
ClinicalTrials.gov Identifier:	NCT00136903

Purpose

To establish the safety and efficacy of two dose levels of Ex-vivo Cultured Adult HumanMesenchymal Stem Cells (Prochymal) in subjects experiencing acute GVHD, Grades II-IV,post HSC transplant.

Condition	Intervention	Phase
Graft vs Host Disease	Drug: Prochymal - 2 million cells Drug: Prochymal - 8 million cells	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase II, Randomized Study to Evaluate the Safety and Efficacy of Prochymal (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) For the Treatment of aGVHD in Patients Who Receive Allogeneic Hematopoietic Stem Cell Transplantation

Further study details as provided by Osiris Therapeutics:

Primary Outcome Measures:

Protocol 260 - Response by Day 28, also called Overall Response. Overall response. includes complete response (CR) and partial response (PR) [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
Protocol 261- Patients were followed for 2 years for safety. The incidence rate of different adverse events among subjects treated with either dose of Prochymal® in the preceding study (Protocol No. 260). [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Protocol 260 - Partial Response or Improvement of GVHD by Day 28 in one or more organs involved with GVHD symptoms at Day 1, [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
Protocol 260 - Time to best response of GVHD [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
Protocol 260 - Time to improvement of GVHD in one or more organs [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
Protocol 261 - Survival through study day 90 [ Time Frame: 90 Days ] [ Designated as safety issue: No ]

Enrollment:	33
Study Start Date:	February 2005
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Prochymal - 2 million cells: Active Comparator Prochymal - 2 million cells/kg actual body weight, intravenously on study Days 1 and 4 plus daily methylprednisolone 2 mg/kg intravenously or prednisone 2.5 mg/kg orally. Subjects will also continue cyclosporine, tacrolimus, and/or MMF at full therapeutic doses	Drug: Prochymal - 2 million cells 2 million cells/kg actual body weight, intravenously on study Days 1 and 4
Prochymal - 8 million cells: Active Comparator Prochymal - 8 million cells/kg actual body weight intravenously on study Days 1 and 4 plus daily methylprednisolone 2 mg/kg intravenously or prednisone 2.5 mg/kg orally. Subjects will also continue cyclosporine, tacrolimus, and/or MMF at full therapeutic doses	Drug: Prochymal - 8 million cells 8 million cells/kg actual body weight intravenously on study Days 1 and 4

Detailed Description:

Protocol 260 - Subjects will be randomized with equal probability to the treatment arms (2 million cells/kg of Prochymal or 8 million cells/kg of Prochymal) using a stratified block design. The stratification factor is acute GVHD grade. For the purpose of stratification, the GVHD grades are II and III-IV. Treatment with investigational agent was administered on study Days 1 and 4. Patients were followed for safety and efficacy until Day 28 after initiation of treatment with the investigational agent, or until withdrawal or death, whichever occurred first.

Protocol 261 - Subjects were evaluated for safety until 2 years from Day 1 of the preceding Prochymal® Protocol No. 260 until withdrawal or death.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Protocol 260 Inclusion Criteria:

Subjects must be 18 to 70 years of age inclusive
If female and of child-bearing age, subjects must be non-pregnant, not breast feeding, and use adequate contraception. Males must use adequate contraception.
Subject must have newly diagnosed, Grade II-IV acute GVHD requiring therapy. Biopsy for confirmation of GVHD is not mandatory, but is recommended when feasible. Enrollment should not be delayed awaiting biopsy results.
Subject must have received either full or reduced intensity myeloablative regimens followed by an allogeneic hematopoietic stem cell transplant using bone marrow, peripheral blood stem cell, or cord blood, including DLI
Subjects must have minimal renal and hepatic function as defined by:

* Calculated creatinine clearance (CLcr) of > 30 mL/min using the Cockroft-Gault equation
Subject must be available for all specified assessments at the study site through study Day 28.
Subjects must provide written informed consent and authorization for use and disclosure of protected health information (PHI).

Protocol 260 Exclusion Criteria:

Subject has received previous treatment for Grade II-IV acute GVHD (except as noted in criterion 2).
Subject has been treated for GVHD with methylprednisolone, > 2mg/kg/day, for more than 72 hours prior to receiving Prochymal™
Subject has uncontrolled alcohol or substance abuse within 6 months of randomization.
Subject has received an investigational agent (not approved by FDA for marketed use in any indication) within 30 days of randomization. Subjects may not receive an investigational agent during the 28-day study period
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 (e.g., uncontrolled infection, right heart failure, pulmonary hypertension, etc.)
Subject has unstable arrhythmia
Subject is unwilling to sign consent form for the long-term follow-up study, protocol No. 261
Subject has a known allergy to bovine or porcine products.
Subject had received transplant for a solid tumor disease.

Protocol 261 Inclusion Criteria:

Subject must have received any treatment with the Investigational Agent in the preceding Prochymal® study.
Subject must have completed their participation in a preceding Prochymal® study.
If female and of child-bearing age, subjects must be non-pregnant, not breast-feeding, and use adequate contraception. Male subjects must use adequate contraception.
Subject must provide written informed consent and written authorization for disclosure and use of PHI.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00136903

Locations

United States, Indiana
St. Francis Hospital
Indianapolis, Indiana, United States, 46237
United States, Missouri
Kansas City Cancer Centers - BMT
Kansas City, Missouri, United States, 64111
United States, New Jersey
The Cancer Center at Hackensack University
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
University of Rochester
Rochester, New York, United States, 14642
New York Medical College
Valhalla, New York, United States, 10595
Mt. Sinai Hospital
New York, New York, United States, 10029
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
Medical College of Wisconsin, FEC
Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Osiris Therapeutics

Investigators

Principal Investigator:

Philip McCarthy, MD

Roswell Park Cancer Institute

More Information

Additional Information:

Click here for more information on Prochymal for treatment of GVHD This link exits the ClinicalTrials.gov site

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.

Responsible Party:	Osiris Therapeutic's Inc. ( Rod Monroy, Ph.D./Sr. Director )
Study ID Numbers:	260-261
Study First Received:	August 25, 2005
Last Updated:	September 3, 2009
ClinicalTrials.gov Identifier:	NCT00136903 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Osiris Therapeutics:

Graft vs Host Disease
GVHD
Graft Versus Host Disease
Bone marrow transplant
Stem cells

Mesenchymal stem cells
Adult stem cells
Leukemia
Lymphoma

Additional relevant MeSH terms:

Immune System Diseases
Graft vs Host Disease

ClinicalTrials.gov processed this record on February 08, 2010