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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00366145




Registration number
NCT00366145
Ethics application status
Date submitted
17/08/2006
Date registered
21/08/2006
Date last updated
10/02/2022

Titles & IDs
Public title
Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease (GVHD)
Scientific 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
Secondary ID [1] 0 0
280
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Graft Versus Host Disease 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Prochymal®
Treatment: Drugs - Placebo
Treatment: Drugs - Standard of Care for GVHD

Active comparator: Prochymal® - Participants who receive standard of care plus treatment with ex vivo cultured adult human mesenchymal stem cells.

Placebo comparator: Placebo - Participants who receive standard of care and do not receive treatment with ex vivo cultured adult human mesenchymal stem cells.


Treatment: Other: Prochymal®
2 infusions of 2 million cells/kg per week for 4 weeks

Treatment: Drugs: Placebo
2 infusions per week for 4 weeks

Treatment: Drugs: Standard of Care for GVHD
Institutionally defined standard of care (e.g., maintenance of steroid treatment and the addition of a second-line therapy)
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants achieving Complete Response of Greater Than or Equal to 28 Days Duration
Timepoint [1] 0 0
up to 100 Days post first infusion
Secondary outcome [1] 0 0
Overall Survival at 180 days Post First Infusion
Timepoint [1] 0 0
Day 180

Eligibility
Key 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.
Minimum age
6 Months
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/08/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/05/2009
Sample size
Target
Accrual to date
Final
260
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane Hospital - Herston
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment postcode(s) [3] 0 0
6100 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Iowa
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United States of America
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Kansas
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United States of America
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Kentucky
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United States of America
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Louisiana
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
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Mississippi
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United States of America
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Nebraska
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New Jersey
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New York
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North Carolina
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Oregon
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Pennsylvania
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South Carolina
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United States of America
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Texas
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Virginia
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Washington
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United States of America
State/province [28] 0 0
Wisconsin
Country [29] 0 0
Canada
State/province [29] 0 0
Alberta
Country [30] 0 0
Canada
State/province [30] 0 0
British Columbia
Country [31] 0 0
Canada
State/province [31] 0 0
Manitoba
Country [32] 0 0
Canada
State/province [32] 0 0
Nova Scotia
Country [33] 0 0
Canada
State/province [33] 0 0
Ontario
Country [34] 0 0
Canada
State/province [34] 0 0
Quebec
Country [35] 0 0
Italy
State/province [35] 0 0
PU
Country [36] 0 0
Italy
State/province [36] 0 0
Pavia
Country [37] 0 0
Switzerland
State/province [37] 0 0
Basel
Country [38] 0 0
United Kingdom
State/province [38] 0 0
England
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Oxford
Country [40] 0 0
United Kingdom
State/province [40] 0 0
UK

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Mesoblast, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00366145
Trial related presentations / 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. doi: 10.1016/s0301-472x(01)00769-x.
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.
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.
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.
Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45. doi: 10.1080/14653240510018118.
Camilleri ET, Gustafson MP, Dudakovic A, Riester SM, Garces CG, Paradise CR, Takai H, Karperien M, Cool S, Sampen HJ, Larson AN, Qu W, Smith J, Dietz AB, van Wijnen AJ. Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production. Stem Cell Res Ther. 2016 Aug 11;7(1):107. doi: 10.1186/s13287-016-0370-8.
Public notes

Contacts
Principal investigator
Name 0 0
Christopher James, PA
Address 0 0
Mesoblast, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00366145