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

Primary Purpose

Graft Vs Host Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Prochymal® - 2 Million cells/kg
Prochymal®- 8 Million cells/kg
Methylprednisolone
Prednisone
Cyclosporine
Tacrolimus
Mycophenolate Mofetil
Sponsored by
Mesoblast, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Vs Host Disease focused on measuring Graft vs Host Disease, (GVHD), Graft Versus Host Disease, Bone marrow transplant, Stem cells, Mesenchymal stem cells (MSCs), Adult stem cells, Leukemia, Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Protocol 260 Inclusion Criteria: 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). Protocol 260 Exclusion Criteria: 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.

Sites / Locations

  • St. Francis Hospital
  • Kansas City Cancer Centers - BMT
  • The Cancer Center at Hackensack University
  • Roswell Park Cancer Institute
  • Mt. Sinai Hospital
  • University of Rochester
  • New York Medical College
  • MD Anderson Cancer Center
  • Medical College of Wisconsin, FEC

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Prochymal® - 2 Million cells/kg

Prochymal® - 8 Million cells/kg

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Protocol 260 - Response by Day 28, also called Overall Response (OR). OR includes complete response (CR) and partial response (PR)
Protocol 261-The incidence rate of different adverse events among participants treated with either dose of Prochymal® in the preceding study (Protocol No. 260).

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,
Protocol 260 - Time to best response of GVHD
Protocol 260 - Time to improvement of GVHD in one or more organs
Protocol 261 - Survival through study day 90

Full Information

First Posted
August 25, 2005
Last Updated
January 14, 2022
Sponsor
Mesoblast, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00136903
Brief Title
Safety and Efficacy Study of Adult Human Mesenchymal Stem Cells to Treat Acute Graft Versus Host Disease (GVHD)
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
April 27, 2005 (Actual)
Primary Completion Date
July 28, 2006 (Actual)
Study Completion Date
July 14, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mesoblast, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Protocol 260 - Participants will be randomized with equal probability to the treatment arms (2 million cells/kilogram (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 will be administered on study Days 1 and 4. Participants will be followed for safety and efficacy until Day 28 after initiation of treatment with the investigational agent, or until withdrawal or death, whichever occurs first. Protocol 261- This study is designed as a long-term safety follow-up of participants who take part in the preceding clinical study of Prochymal® (Protocol 260) for the treatment of acute GVHD. Participants will be enrolled in Study 261 upon completion of the preceding Study 260.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prochymal® - 2 Million cells/kg
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Prochymal® - 8 Million cells/kg
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Prochymal® - 2 Million cells/kg
Other Intervention Name(s)
Remestemcel-L, ex-vivo cultured adult human mesenchymal stem cells, hMSCs
Intervention Description
2 million hMSCs/kg actual body weight, IV on study Days 1 and 4
Intervention Type
Drug
Intervention Name(s)
Prochymal®- 8 Million cells/kg
Other Intervention Name(s)
Remestemcel-L, ex-vivo cultured adult human mesenchymal stem cells, hMSCs
Intervention Description
8 million hMSCs/kg actual body weight IV on study Days 1 and 4
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Description
Methylprednisolone 2 mg/kg administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone 2.5 mg/kg administered orally.
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Intervention Description
Administered as prescribed by the caregiver.
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Intervention Description
Administered as prescribed by the caregiver.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Intervention Description
Administered as prescribed by the caregiver.
Primary Outcome Measure Information:
Title
Protocol 260 - Response by Day 28, also called Overall Response (OR). OR includes complete response (CR) and partial response (PR)
Time Frame
28 Days
Title
Protocol 261-The incidence rate of different adverse events among participants treated with either dose of Prochymal® in the preceding study (Protocol No. 260).
Time Frame
2 Years
Secondary Outcome Measure Information:
Title
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
Title
Protocol 260 - Time to best response of GVHD
Time Frame
28 Days
Title
Protocol 260 - Time to improvement of GVHD in one or more organs
Time Frame
28 Days
Title
Protocol 261 - Survival through study day 90
Time Frame
90 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Protocol 260 Inclusion Criteria: 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). Protocol 260 Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher James, PA
Organizational Affiliation
Mesoblast, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
St. Francis Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
Kansas City Cancer Centers - BMT
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
The Cancer Center at Hackensack University
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Mt. Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Medical College of Wisconsin, FEC
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11823036
Citation
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.
Results Reference
background
PubMed Identifier
10989188
Citation
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.
Results Reference
background
PubMed Identifier
15846293
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. doi: 10.1016/j.bbmt.2005.02.001.
Results Reference
background
PubMed Identifier
15121408
Citation
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.
Results Reference
background
PubMed Identifier
16040382
Citation
Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45. doi: 10.1080/14653240510018118.
Results Reference
background
PubMed Identifier
19539211
Citation
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.
Results Reference
result
Links:
URL
http://www.osiristx.com
Description
Click here for more information on Prochymal® for treatment of GVHD

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

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