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

NCT00136903 | Completed Phase 2 FDA Drug

• 1 other identifier: 260-261
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 9

Brief Summary

To establish the safety and efficacy of two dose levels of ex-vivo cultured adult human mesenchymal stem cells (hMSCs) (Prochymal®) in participants experiencing acute GVHD, Grades II-IV, post hematopoietic stem cells (HSC) transplant.

Conditions

Graft Vs Host Disease

Keywords

Graft vs Host Disease; (GVHD); Graft Versus Host Disease; Bone marrow transplant; Stem cells; Mesenchymal stem cells (MSCs); Adult stem cells; Leukemia; Lymphoma

Outcome Measures

Primary Outcomes (2)

• Protocol 260 - Response by Day 28, also called Overall Response (OR). OR includes complete response (CR) and partial response (PR)

  28 Days

• Protocol 261-The incidence rate of different adverse events among participants treated with either dose of Prochymal® in the preceding study (Protocol No. 260).

  2 Years

Secondary Outcomes (4)

• Protocol 260 - Partial Response or Improvement of GVHD by Day 28 in one or more organs involved with GVHD symptoms at Day 1,

  28 Days

• Protocol 260 - Time to best response of GVHD

  28 Days

• Protocol 260 - Time to improvement of GVHD in one or more organs

  28 Days

• Protocol 261 - Survival through study day 90

  90 Days

Study Arms (2)

Prochymal® - 2 Million cells/kg

ACTIVE COMPARATOR

Participants will receive Prochymal® consisting of 2 million hMSCs/kg actual body weight, intravenously (IV) on Days 1 and 4 along with daily standard of care which includes methylprednisolone 2 milligrams (mg)/kg IV or prednisone 2.5 mg/kg orally. Participants will also continue cyclosporine, tacrolimus, and/or mycophenolate mofetil (MMF) at full therapeutic doses.

Drug: Prochymal® - 2 Million cells/kg; Drug: Methylprednisolone; Drug: Prednisone; Drug: Cyclosporine; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

Prochymal® - 8 Million cells/kg

ACTIVE COMPARATOR

Participants will receive Prochymal® consisting of 8 million hMSCs/kg actual body weight IV on Days 1 and 4 along with daily standard of care which includes methylprednisolone 2 mg/kg IV or prednisone 2.5 mg/kg orally. Participants will also continue cyclosporine, tacrolimus, and/or mycophenolate mofetil (MMF) at full therapeutic doses.

Drug: Prochymal®- 8 Million cells/kg; Drug: Methylprednisolone; Drug: Prednisone; Drug: Cyclosporine; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

Interventions

Prochymal® - 2 Million cells/kg DRUG

2 million hMSCs/kg actual body weight, IV on study Days 1 and 4

Also known as: Remestemcel-L, ex-vivo cultured adult human mesenchymal stem cells, hMSCs

Prochymal® - 2 Million cells/kg

Prochymal®- 8 Million cells/kg DRUG

8 million hMSCs/kg actual body weight IV on study Days 1 and 4

Also known as: Remestemcel-L, ex-vivo cultured adult human mesenchymal stem cells, hMSCs

Prochymal® - 8 Million cells/kg

Methylprednisolone DRUG

Methylprednisolone 2 mg/kg administered intravenously.

Prochymal® - 2 Million cells/kg; Prochymal® - 8 Million cells/kg

Prednisone DRUG

Prednisone 2.5 mg/kg administered orally.

Prochymal® - 2 Million cells/kg; Prochymal® - 8 Million cells/kg

Cyclosporine DRUG

Administered as prescribed by the caregiver.

Prochymal® - 2 Million cells/kg; Prochymal® - 8 Million cells/kg

Tacrolimus DRUG

Administered as prescribed by the caregiver.

Prochymal® - 2 Million cells/kg; Prochymal® - 8 Million cells/kg

Mycophenolate Mofetil DRUG

Administered as prescribed by the caregiver.

Prochymal® - 2 Million cells/kg; Prochymal® - 8 Million cells/kg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 to 70 years of age inclusive.
• If female and of child-bearing age, participant must be non-pregnant, not breast feeding, and use adequate contraception. Males must use adequate contraception.
• Participant 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.
• Participant 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).
• Participant must have minimal renal and hepatic function as defined by:
• \* Calculated creatinine clearance (CLcr) of \> 30 mL/min using the Cockroft-Gault equation.
• Participant must be available for all specified assessments at the study site through study Day 28.
• Participant must provide written informed consent and authorization for use and disclosure of protected health information (PHI).

You may not qualify if:

• Participant has received previous treatment for Grade II-IV acute GVHD (except as noted in Criterion 2).
• Participant has been treated for GVHD with methylprednisolone, \> 2mg/kg/day, for more than 72 hours prior to receiving Prochymal®.
• Participant has uncontrolled alcohol or substance abuse within 6 months of randomization.
• Participant has received an investigational agent (not approved by food and drug administration (FDA) for marketed use in any indication) within 30 days of randomization. Participant may not receive an investigational agent during the 28-day study period.
• 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 (e.g., uncontrolled infection, right heart failure, pulmonary hypertension, etc.).
• Participant has unstable arrhythmia.
• Participant is unwilling to sign consent form for the long-term follow-up study, Protocol 261.
• Participant has a known allergy to bovine or porcine products.
• Participant had received transplant for a solid tumor disease.

Sponsors & Collaborators

• Mesoblast, Inc.: lead

Study Sites (9)

St. Francis Hospital

Indianapolis, Indiana, 46237, United States

Location

Kansas City Cancer Centers - BMT

Kansas City, Missouri, 64111, United States

Location

The Cancer Center at Hackensack University

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Mt. Sinai Hospital

New York, New York, 10029, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin, FEC

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (6)

• 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. doi: 10.1016/s0301-472x(01)00769-x.

  PMID: 11823036 BACKGROUND

• Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000 Aug;28(8):875-84. doi: 10.1016/s0301-472x(00)00482-3.

  PMID: 10989188 BACKGROUND

• 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. doi: 10.1016/j.bbmt.2005.02.001.

  PMID: 15846293 BACKGROUND

• 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. doi: 10.1016/S0140-6736(04)16104-7.

  PMID: 15121408 BACKGROUND

• Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45. doi: 10.1080/14653240510018118.

  PMID: 16040382 BACKGROUND

• 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.

  PMID: 19539211 RESULT

Related Links

• Click here for more information on Prochymal® for treatment of GVHD

MeSH Terms

Conditions

Graft vs Host Disease; Leukemia; Lymphoma

Interventions

remestemcel-l; Methylprednisolone; Prednisone; Cyclosporine; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Christopher James, PA

  Mesoblast, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2005
• First Posted: August 29, 2005
• Study Start: April 27, 2005
• Primary Completion: July 28, 2006
• Study Completion: July 14, 2008
• Last Updated: January 31, 2022

Record last verified: 2022-01

Locations

US (9)