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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00562497




Registration number
NCT00562497
Ethics application status
Date submitted
20/11/2007
Date registered
22/11/2007
Date last updated
19/01/2022

Titles & IDs
Public title
Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed 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® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute GVHD
Secondary ID [1] 0 0
265
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: Drugs - Prochymal®
Other interventions - Placebo
Other interventions - Corticosteroid

Placebo Comparator: Placebo - Participants will receive 6 infusions of placebo-matching Prochymal® intravenously (IV) during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28.

Active Comparator: Prochymal® 2x10^6 hMSC/kg - Participants will receive 6 infusions of Prochymal® 2x10^6 human mesenchymal stem cells (hMSC)/kg IV during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28.


Treatment: Drugs: Prochymal®
Prochymal® intravenous infusion.

Other interventions: Placebo
Placebo-matching Prochymal® intravenous infusion.

Other interventions: Corticosteroid
Administration will be intravenously as prescribed by the caregiver.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Treatment Success
Timepoint [1] 0 0
90 Days
Secondary outcome [1] 0 0
Percentage of Participants with Overall Response
Timepoint [1] 0 0
Day 90
Secondary outcome [2] 0 0
Percentage of Participants with Induction of a 2-grade decrease in (Graft Versus Host Disease) GVHD by Study Day 28 with maintenance of a 2-grade decrease in GVHD through Study Day 56
Timepoint [2] 0 0
Up to Day 56
Secondary outcome [3] 0 0
Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days
Timepoint [3] 0 0
Day 14
Secondary outcome [4] 0 0
Percentage of Participants with Induction of a CR after Study Day 28 and clinically managed with steroids with second line/escalation therapy through Study Day 56
Timepoint [4] 0 0
Up to Day 56
Secondary outcome [5] 0 0
Percentage of Participants with Induction of PR during the first 28 days
Timepoint [5] 0 0
Up to Day 28
Secondary outcome [6] 0 0
Time to achieve CR
Timepoint [6] 0 0
Up to Day 90
Secondary outcome [7] 0 0
Number of CR per organ
Timepoint [7] 0 0
Up to Day 90
Secondary outcome [8] 0 0
Total corticosteroid dose administered
Timepoint [8] 0 0
Up to Day 90
Secondary outcome [9] 0 0
Number of corticosteroid-related complications
Timepoint [9] 0 0
Up to Day 90
Secondary outcome [10] 0 0
Number of Infectious complications
Timepoint [10] 0 0
Up to Day 90
Secondary outcome [11] 0 0
Number of Days of Hospitalization
Timepoint [11] 0 0
Up to Day 90
Secondary outcome [12] 0 0
Average Daily Corticosteroid Dose
Timepoint [12] 0 0
Up to Day 90

Eligibility
Key inclusion criteria
- Participants must be 18 years to 70 years of age, inclusive

- Participants must have received an allogeneic hematopoietic stem cell transplant using
either bone marrow, peripheral blood stem cells or cord blood or administered a donor
leukocyte infusion.

- Participants must have newly diagnosed Grades B-D acute GVHD. Biopsy confirmation of
GVHD is strongly recommended but not required. Randomization should not be delayed
awaiting biopsy or pathology results.

- Participants must be randomized and treated with corticosteroid (1-2 mg/kg/d
methylprednisolone, or equivalent) and Prochymal®/placebo within 72 hours of onset of
acute GVHD.

- Participants must have adequate renal function as defined by: Calculated Creatinine
Clearance of >30 mL/min using the Cockcroft-Gault equation

- 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
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participant has been previously treated with systemic immunosuppressive therapy for
acute GVHD

- 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.

- Participants may not receive any other investigational agents (not approved by the FDA
for any indication) concurrently during study participation or within 30 days of
randomization.

- Participant has a known allergy to bovine or porcine products or dimethyl sulfoxide
(DMSO)

- Participant has received a transplant for a solid tumor disease.

- Participant requires more than 2 liters/min of oxygen to maintain stable oxygen
saturation (Sa02) greater than or equal to 92%

- Participant requires a renal dopamine dose greater than 1-3 mcg/kg/min to maintain
renal blood flow associated with renal failure and improved urinary output.

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 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
31/01/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/05/2010
Sample size
Target
Accrual to date
Final
192
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [4] 0 0
St. Vincent's Hospital - Darlinghurst
Recruitment hospital [5] 0 0
Royal Brisbane Hospital - Herston
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment postcode(s) [3] 0 0
6001 - Perth
Recruitment postcode(s) [4] 0 0
NSW 2010 - Darlinghurst
Recruitment postcode(s) [5] 0 0
QLD 4029 - Herston
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Mississippi
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
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Ohio
Country [17] 0 0
United States of America
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Pennsylvania
Country [18] 0 0
United States of America
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South Carolina
Country [19] 0 0
United States of America
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Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Canada
State/province [23] 0 0
Alberta
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase III, randomized, double-blind, placebo-controlled study to investigate the
efficacy and safety of Prochymal® versus placebo in combination with corticosteroids as
initial therapy for acute GVHD. Corticosteroids have been the primary therapy for patients
with previously untreated acute GVHD and the historical published data define an expected 35%
complete response (CR) at Day +28 using this therapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00562497
Trial related presentations / publications
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/ct2/show/NCT00562497