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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00366145
Recruitment Status : Completed
First Posted : August 21, 2006
Last Update Posted : February 10, 2022
Sponsor:
Information provided by (Responsible Party):
Mesoblast, Ltd. ( Mesoblast, Inc. )

Study Description
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Brief Summary:
The purpose of this study is to evaluate the efficacy and gather additional safety information for Prochymal® in participants 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: Prochymal® Drug: Placebo Drug: Standard of Care for GVHD Phase 3

Detailed Description:
Approximately 6300 patients receive allogeneic hematopoietic stem cell transplants in the United States each year (International Bone Marrow Transplant Registry [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 will 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. Participants 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 : 260 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 Patients Who Have Failed to Respond to Steroid Treatment for Acute GVHD
Actual Study Start Date : August 17, 2006
Actual Primary Completion Date : December 26, 2008
Actual Study Completion Date : May 28, 2009

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Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Prochymal®
Participants who receive standard of care plus treatment with ex vivo cultured adult human mesenchymal stem cells.
 Biological: Prochymal®
2 infusions of 2 million cells/kg per week for 4 weeks
Other Name: Mesenchymal Stem Cells

Drug: Standard of Care for GVHD
Institutionally defined standard of care (e.g., maintenance of steroid treatment and the addition of a second-line therapy)
Placebo Comparator: Placebo
Participants who receive standard of care and do not receive treatment with ex vivo cultured adult human mesenchymal stem cells.
 Drug: Placebo
2 infusions per week for 4 weeks
Other Name: excipients without adult human mesenchymal stem cells

Drug: Standard of Care for GVHD
Institutionally defined standard of care (e.g., maintenance of steroid treatment and the addition of a second-line therapy)


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants achieving Complete Response of Greater Than or Equal to 28 Days Duration [ Time Frame: up to 100 Days post first infusion ]
    A complete response was defined as complete resolution of all clinical signs of Graft versus host disease (GVHD)- that had to be maintained for at least 28 consecutive days (durable complete response [DCR]) within 100 days post first infusion.


Secondary Outcome Measures :
  1. Overall Survival at 180 days Post First Infusion [ Time Frame: Day 180 ]
    Percentage of participants who survived at 180 days post first infusion.


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

Inclusion Criteria:

  • Participant must be 6 months to 70 years of age, inclusive.
  • Participants 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.
  • Participant 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.
  • Participants 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.
  • Participant must have adequate renal function as defined by: Calculated Creatinine Clearance of >30 milliliters per minute (mL/min) using the Cockcroft-Gault equation.
  • For pediatric participants: Schwartz equation: (Participant population: infants over 1 week old through adolescence (<18 years old).
  • Participants who are women of childbearing potential must be non-pregnant, not breast-feeding, and use adequate contraception. Male participants must use adequate contraception.
  • Participant must have a minimum Karnofsky Performance Level of at least 30 at the time of study entry.
  • Participant (or legal representative where appropriate) must be capable of providing written informed consent.

Exclusion Criteria:

  • Participant has started treatment with second line therapy >24 hours prior to randomization.
  • Participant has received agents other than steroids for primary treatment of acute GVHD.
  • Participant is participating in the CTN Protocol 0302.
  • 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 including uncontrolled infection, heart failure, pulmonary hypertension, etc.
  • Participant may not receive any other investigational agents (not approved by the FDA) concurrently during study participation or within 30 days of randomization.
  • Participant has a known allergy to bovine or porcine products.
  • Participant has received a transplant for a solid tumor disease.
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00366145


Locations
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Sponsors and Collaborators
Mesoblast, Inc.
Investigators
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Study Director: Christopher James, PA Mesoblast, Inc.
More Information
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Additional Information:

Publications:

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

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Responsible Party: Mesoblast, Inc.
ClinicalTrials.gov Identifier: NCT00366145    
Obsolete Identifiers: NCT00476840
Other Study ID Numbers: 280
First Posted: August 21, 2006    Key Record Dates
Last Update Posted: February 10, 2022
Last Verified: February 2022

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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. ):
Acute GVHD
Steroid refractory GVHD
Severe steroid refractory acute GVHD
Steroid refractory
Steroid Refractory Acute Graft Versus Host Disease
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Remestemcel-l
 Anti-Inflammatory Agents
Antiviral Agents
Anti-Infective Agents