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

• ClinicalTrials.gov Identifier: NCT00136903
• Recruitment Status: Completed
• First Posted: August 29, 2005
• Last Update Posted: March 9, 2020
• Sponsor: Mesoblast, Inc.
• Information provided by (Responsible Party): Mesoblast, Ltd. ( Mesoblast, Inc. )

Study Description

Brief Summary:

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 hematopoietic stem cells (HSC) transplant.

Condition or disease	Intervention/treatment	Phase
Graft Vs Host Disease	Drug: Prochymal - 2 million cells; Drug: Prochymal - 8 million cells	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Acute GVHD in Patients Who Receive Allogeneic Hematopoietic Stem Cell Transplantation
• Actual Study Start Date: April 27, 2005
• Actual Primary Completion Date: July 28, 2006
• Actual Study Completion Date: July 14, 2008

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Prochymal - 2 million cells; 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 mycophenolate mofetil (MMF) at full therapeutic doses	Drug: Prochymal - 2 million cells; 2 million cells/kg actual body weight, intravenously on study Days 1 and 4; Other Names: Ex-vivo Cultured Adult Human Mesenchymal Stem Cells; human mesenchymal stem cells (hMSCs)
Active Comparator: Prochymal - 8 million cells; 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; Other Names: Ex-vivo Cultured Adult Human Mesenchymal Stem Cells; hMSCs

Outcome Measures

Primary Outcome Measures :

1. Protocol 260 - Response by Day 28, also called Overall Response. Overall response. includes complete response (CR) and partial response (PR) [ Time Frame: 28 Days ]
2. 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 ]

Secondary Outcome Measures :

1. 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 ]
2. Protocol 260 - Time to best response of GVHD [ Time Frame: 28 Days ]
3. Protocol 260 - Time to improvement of GVHD in one or more organs [ Time Frame: 28 Days ]
4. Protocol 261 - Survival through study day 90 [ Time Frame: 90 Days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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 donor lymphocyte infusion (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.

Contacts and Locations

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

Mt. Sinai Hospital

New York, New York, United States, 10029

University of Rochester

Rochester, New York, United States, 14642

New York Medical College

Valhalla, New York, United States, 10595

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

Mesoblast, Inc.

Investigators

• Study Director: Mahboob Rahman, MD; Mesoblast, Inc.

More Information

Additional Information:

Click here for more information on Prochymal for treatment of GVHD 

Publications of Results:

Kebriaei P, Isola L, Bahceci E, Holland K, Rowley S, McGuirk J, Devetten M, Jansen J, Herzig R, Schuster M, Monroy R, Uberti J. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009 Jul;15(7):804-11. doi: 10.1016/j.bbmt.2008.03.012.

Other 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.

• Responsible Party: Mesoblast, Inc.
• ClinicalTrials.gov Identifier: NCT00136903
• Obsolete Identifiers: NCT00476762
• Other Study ID Numbers: 260-261
• First Posted: August 29, 2005
• Last Update Posted: March 9, 2020
• Last Verified: March 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mesoblast, Ltd. ( Mesoblast, Inc. ):

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:

Graft vs Host Disease; Immune System Diseases